Case No. 1

• A 63-year-old woman has a 1-month history of dry cough, night sweats, anorexia, and a 50-lb (23-kg) weight loss. She is a nonsmoker. She has type 2 diabetes, dyslipidemia, and hypertension but had stopped all medication 6 months earlier after having a disagreement with her physician. She did not abuse drugs or alcohol, and there was no history of recent travel.

• Other than left basal crackles, results of a physical examination were normal. Other than mild hyponatremia (serum sodium level, 132 and hyperglycemia (glucose level, 490 mg/dL, results of laboratory studies were normal.

• Results of chest radiographs and representative CT images are shown. Bronchoscopy demonstrated no endobronchial lesions, cytologic studies were negative, and cultures grew only normal respiratory flora.

At this point, you would initiate which of the following interventions?

• A. Percutaneous drainage with a pigtail catheter.

• B. Lung resection.

• C. Broad-spectrum antibiotics with anaerobic coverage.

• D. Bronchoscopic abscess drainage.

• The chest radiographs and CT scan show a large left lower lobe lung abscess with irregular thick walls. While the appearance of the abscess could be consistent with a malignancy, the clinical presentation and negative bronchoscopy suggests that this is a pyogenic lung abscess. The lack of treatment for this patient’s diabetes likely played a role. When an endobronchial obstruction has been excluded, a prolonged course of broad-spectrum antibiotics with anaerobic coverage is the standard treatment.

• Only if this regimen fails, drainage or resection options are considered. Percutaneous drainage with a pigtail catheter is one option but is not necessary or indicated at this time. Pneumonostomy or cavernostomy with direct drainage (Monaldi procedure) is another option but is only possible when the pleural space is obliterated. Lung resection is usually reserved for septic complications. These surgical procedures achieved cure rates of 90% but with concomitant mortality rates of

• 11% to 28%.

• More recently, endoscopic drainage of a lung abscess has been introduced. Under fluoroscopic control, a guidewire is introduced into the cavity through the working channel of a flexible bronchoscope. Once the guidewire is confirmed to be in place, the catheter and bronchoscope are removed, and a 90-cm pigtail catheter of at least 7F is slipped over the wire into the cavity. This form of drainage and percutaneous catheter drainage has proven effective in appropriately selected adult and pediatric patients but only if antibiotic therapy has proved unsuccessful.

• Medical therapy is usually successful, and it has been estimated that drainage is required in only 11% to 21% of patients.

• Given the CT appearance of the irregular, thick-walled cavity, careful follow-up will be required to ensure complete resolution.

• Endoscopic drainage can be attempted in select patients who have an airway connection to the abscess. It has an advantage over other procedures in that it does not carry the risk of soiling the pleural space and is less invasive and not associated with the loss of lung parenchyma, as in a surgical resection.

• Oropharyngeal anaerobes and microaerophilic streptococci have been the predominant pathogens involved in lung abscess. In some studies, gram-negative bacteria have been the etiologic agent in as many as 20% of patients. Therefore an appropriate initial treatment regimen would include a third-generation cephalosporin with clindamycin or metronidazole or possibly a -lactam/-lactamase inhibitor alone.

At this point, you would initiate which of the following interventions?

• A. Percutaneous drainage with a pigtail catheter.

• B. Lung resection.

• C. Broad-spectrum antibiotics with anaerobic coverage.

• D. Bronchoscopic abscess drainage.

Case No. 2

• A 68-year-old man is evaluated for a 1-month history of hemoptysis. He had a history of stable schizophrenia,

• untreated COPD, and remote bladder cancer. He had smoked 2 packages of cigarettes daily for the past 32 years but quit 4 months ago due to an increase in his chronic cough and sputum production. He had a chronic cough productive of at least 2 tbsp (30 mL) of thick white-yellow mucus daily going back many years, but for the previous 2 months, he had regular flecks of pinkish material in his sputum. He was otherwise well.

• Physical examination revealed normal vital signs, decreased breath sounds bilaterally, a prolonged forced expiratory time, and high pitched, late expiratory wheezes most marked over the upper lobes. Results of preliminary blood work, including a CBC, prothrombin time, and partial thromboplastin time, were all normal. He had a FEV1 of 1.1 L (55% of predicted) and FVC of 2.7 L (95% of predicted), with an FEV1/FVC of 0.40 and no response to inhaled bronchodilator. He had hyperinfl ation, gas trapping, and a Dlco of 53% of predicted

CT after 2 months

Which of the following is most true about this condition?

• A. It has a high malignant potential.

• B. It is a consequence of granulomatous infl ammation.

• C. Th oracotomy for removal is the treatment of choice.

• D. It is more commonly found in the left lung.

• The initial CT scan reveals protrusion of a calcified lesion into the bronchus intermedius. Bronchoscopy reveals a whitish lesion protruding through the wall of the bronchus intermedius. Finally, the repeat CT scan after 2 months shows migration of the calcification into the right lower lobe bronchus. It can no longer be seen in the bronchus intermedius and now occludes the lateral and posterior segmental bronchi to the right lower lobe. Together, these findings are diagnostic of broncholithiasis. This most commonly occurs as a result of infection with Mycobacterium tuberculosis or Histoplasma capsulatum. A repeat bronchoscopy confirms migration of the broncholith to the right lower lobe.

• Broncholithiasis is defined as the presence of calcified or ossified material within the lumen of the bronchus. Most broncholiths originate as calcifications of peribronchial lymph nodes that subsequently erode into the airway. These lymph nodes calcify after an inflammatory process usually initiated by infection.

• TB is the most common cause of broncholiths.

• Broncholiths are much more common on the right side perhaps related to the fact that lymphatic drainage of the lung eventually reaches the right paratracheal and azygous nodes. The most common symptoms include cough and hemoptysis and, occasionally, actual stones are coughed up (lithoptysis).

• Patients may develop recurrent pneumonias from occluding stones, and the latter may migrate, as occurred in this patient. Although calcifi ed tumors, such as carcinoids, hamartomas, or osteosarcomas, may mimic broncholiths, the latter do not have increased malignant potential.

• Flexible bronchoscopy can be utilized to visualize the lesion but does not have a therapeutic role. Rigid bronchoscopy can be used to remove stones occasionally with the aid of neodymium-doped yttrium aluminum garnet lasers. Older research cautioned against bronchoscopic removal of broncholiths because of concern for inducing massive hemoptysis/hemorrhage.

• Thoracotomy with segmental or lobar resection was the procedure of choice. However, more recent literature has clearly shown that the majority of broncholiths seen in the airway are mobile and can be removed bronchoscopically, with thoracotomy reserved for the minority of patients in whom the broncholiths are adherent to the mucosa.

• Asymptomatic broncholiths do not require therapy, and patient observation alone is recommended.

Which of the following is most true about this condition?

• A. It has a high malignant potential.

• B. It is a consequence of granulomatous infl ammation.

• C. Th oracotomy for removal is the treatment of choice.

• D. It is more commonly found in the left lung.

Case No. 3

• A 25-year-old woman, primigravida, in her 25th week of pregnancy is seen in your office for worsening asthma. She has had asthma since childhood, which has been managed with good control with fluticasone, 250 ug 2 puff s bid, and salmeterol, 50 ug 1 puff bid, as well as prn salbutamol.

• She now reports several weeks of nightly nocturnal awakenings with wheezing, cough, and chest tightness and is using her albuterol inhaler more than 4 times a day. She denies symptoms of gastroesophageal reflux.

• On physical examination, she is in no respiratory distress with stable vital signs. Her respiratory rate is 15/min. She is not using external muscles of accessory ventilation. She is afebrile. Her lung examination reveals diff use wheezing, but with preserved air movement, and her abdominal examination is notable for a gravid appearance. Her peak flow rates are approximately 60% of her personal best.

In addition to asthma education, the next best step in her management would be which of the following?

• A. Begin oral corticosteroids.

• B. Begin tiotropium

• C. Double the dose of inhaled corticosteroids.

• D. Change fluticasone to budesonide.

• Asthma aff ects up to 8% of pregnant women and, if poorly controlled, can result in increased fetal and maternal morbidity, including increased risks of preterm labor, preeclampsia, congenital anomalies, intrauterine growth retardation, and placenta previa.

• In general, the course of asthma in pregnancy can be divided into thirds, with one third of patients improving, one-third worsening, and one-third remaining at baseline. The severity of asthma in prior pregnancies and in the nonpregnant state are good predictors of the course of asthma in pregnancy. Asthma tends to be worse in the middle of pregnancy (gestational weeks 17 to 36) and better in the first and latter third trimesters.

• Gastroesophageal reflux, sinusitis, and allergic rhinitis, leading to worsening asthma, should be carefully evaluated in a pregnant woman who has asthma.

• The treatment of chronic asthma in pregnancy is generally similar to that of the patient with asthma who is not pregnant. The National Asthma Education Program sponsored by the National Heart, Lung, and Blood Institute developed guidelines for the treatment of the pregnant person with asthma, subsequently revised in 2004 and 2007.

• In general, patients with asthma whose asthma is well controlled on an appropriate medical regimen prior to pregnancy can remain on this regimen if control is acceptable during pregnancy. This woman is a moderately controlled (moderate persistent) asthmatic who now is falling into the poorly controlled (severe persistent) category, with frequent nocturnal awakenings and increased use of albuterol rescue therapy. Systemic corticosteroids would be indicated at this point in this patient as in a nonpregnant asthmatic.

• Systemic corticosteroids are category C agents. There have been several studies examining the effects of corticosteroids in pregnancy. Initial studies suggested that systemic corticosteroids were associated with prematurity, infants with low birth weight, and an increase in congenital malformations, including cleft palate. However, further review of these studies postulated that poorly controlled asthma was the cause of the majority of these abnormalities. Patients receiving systemic corticosteroids require careful evaluation for gestational diabetes. In the patient with asthma who is corticosteroid dependent, stressdose corticosteroids should be administered during labor and delivery.

• Short-acting selective 2-agonists are indicated for well-controlled (mild intermittent) asthma (albuterol has been the drug most widely studied in pregnancy, and is the preferred agent). Low-dose inhaled corticosteroids are the preferred agent for initiating treatment for partially controlled asthma (mild persistent) in the pregnant patient.

• Budesonide (category B) and beclomethasone (category C) are the best-studied inhaled corticosteroids, and budesonide is the preferred agent. Patients whose condition is being successfully controlled with other inhaled corticosteroids can continue using these agents.

• Alternative treatments include leukotriene receptor antagonists (not zileuton) or low dose theophylline. For those whose asthma is less well controlled (moderate persistent asthma), a medium dose inhaled steroid or low-dose steroid with a long-acting β-agonist (salmeterol is preferred due to adequacy of studies) is recommended. Poorly controlled (severe persistent) asthma should be managed with high-dose inhaled corticosteroids and a long-acting β 2-agonist, as with this patient, and an oral corticosteroid should be added if needed.

• Short-acting selective 2-agonists are category C agents. Inhaled corticosteroids are category B (budesonide) and C (all other inhaled corticosteroids) agents. Salmeterol and formoterol are category C agents. Th eophylline is a category C agent. The leukotriene antagonists, montelukast and zafirlukast, although not well studied in pregnancy, are category B agents.

• Zileuton (category C) is the least well studied and should be avoided.

• Th e other choices listed, although permitted during pregnancy, would not be appropriate in a patient who now has worsening asthma. Th e patient is already on a reasonable dose of inhaled corticosteroids and doubling the dose would likely be of little benefit, although an increase in her maintenance dose may be required once the exacerbation is better controlled (choice C is incorrect). Although recent data may suggest a benefit of tiotropium in asthma, this is a category C agent with minimal data for use in pregnancy.

• Changing to the category B inhaled corticosteroid would not be indicated to improve poorly controlled asthma, and a change in inhaled steroid because of pregnancy is not recommended in patients already on an inhaled corticosteroid regimen.

In addition to asthma education, the next best step in her management would be which of the following?

• A. Begin oral corticosteroids.

• B. Begin tiotropium

• C. Double the dose of inhaled corticosteroids.

• D. Change fluticasone to budesonide.

Case No. 4

• A 19-year-old man is referred to you for assessment of possible pulmonary arteriovenous malformations (PAVMs). The patient’s father was recently diagnosed with hereditary hemorrhagic telangiectasia (HHT) after having hemoptysis. The father was subsequently documented to have pulmonary arteriovenous malformations, and the diagnosis was confi rmed by genetic testing. The son denies any symptoms and is a lifelong nonsmoker. He gets occasional nosebleeds, but they are mild and stop spontaneously. He denies any shortness of breath or activity limitation. He also denies any hematemesis, melena, or hematochezia. The remainder of the history is noncontributory.

• Physical examination reveals mucosal and cutaneous telangiectasia. There is no clubbing, cyanosis, pallor, or jaundice. Oxygen saturation on room air is 98%. Results of a chest examination are normal, and the rest of the physical examination results are normal. The patient’s hemoglobin level is 13.9 g/dL. Results of liver enzymes and function tests are normal. The patient’s chest radiograph is reported normal with no evidence of nodules, masses, or feeding vessels.

Which would be the next most appropriate step to assess for the presence of PAVMs?

• A. Measurement of the physiologic shunt fraction.

• B. Pulmonary angiography.

• C. CT chest angiography.

• D. Contrast echocardiography.

• This patient has a high clinical suspicion for HHT (Osler-Rendu-Weber Syndrome) with a confirmed positive family history, nosebleeds, mucosal and cutaneous telangiectasia, and anemia. It would be important to confirm the diagnosis of HHT with genetic testing. While the chest radiograph is normal, the next most important clinical step is to assess for possible PAVMs. All patients with possible or confirmed HHT should be actively screened for PAVMs.

• While careful clinical examination should routinely be undertaken, only 10% of affected patients have cyanosis, clubbing, and/or a pulmonary bruit. The screening technique of choice is contrast echocardiography with agitated saline, which is more sensitive than oxygen shunt testing.

• CT scanning should not routinely be used for screening because of the associated radiation exposure (choice C is incorrect) unless expertise in transthoracic contrast echocardiography is not readily available. Pulmonary angiography has a lower resolution than current multidetector CT scanning and should not be performed as a screening procedure.

• PAVMs are present in approximately 15% to 50% of people with HHT. Acknowledging the risk and the frequency of serious complications, all patients with HHT should be screened for pulmonary and cerebral arteriovenous malformations. Complications include life-threatening hemorrhage and neurologic complications. Stroke has been reported in 10% to 36% of patients, transient ischemic attack in 6% to 37%, cerebral abscess in 8% to 19%, and massive hemoptysis or spontaneous hemothorax in 4% to 20%. Th e hemorrhagic complications of PAVMs can be life threatening, and the risk appears to be increased during pregnancy.

Which would be the next most appropriate step to assess for the presence of PAVMs?

• A. Measurement of the physiologic shunt fraction.

• B. Pulmonary angiography.

• C. CT chest angiography.

• D. Contrast echocardiography.

Case No. 5

Mutations of which of the following genes are common in heritable pulmonary arterial hypertension?

• A. Toll-like receptor (TLR).

• B. Bone morphogenetic protein receptor II (BMPR2).

• C. Protease inhibitor (PI ).

• D. Epidermal growth factor receptor (EGFR).

• DNA specimens from families with pulmonary arterial hypertension (PAH) are commonly found to have mutations in the gene on chromosome 2q32 that encodes bone morphogenetic protein receptor II (BMPR2 ); these genotypes occur in 80% of families with heritable PAH (choice B is correct). Although this is an autosomal dominant disorder, it is expressed in only 20% of carriers, presumably related to environmental factors or other genetic modifi ers.

• Genomics refers to the study of the genome that arose from technologies that map and sequence genes and their relationships to cellular and molecular biology. Proteomics, a related discipline, is the study of proteins, how they are modified and expressed, and how they are involved in metabolic pathways and other proteins.

• Well-known examples of genomic techniques that elucidated mechanisms of disease include identifying mutations in the cystic fibrosis transmembrane receptor (CTFR) in cystic fibrosis and the protease inhibitor (PI ) gene in 1-antiprotease deficiency.

• Similarly, specific genetic variations in the Toll-like receptor pathway (TLR) predict poor outcomes in sepsis (choice A is incorrect), and mutations of the epidermal growth factor receptor (EGFR) gene identify a subset of patients with adenocarcinoma of the lung who may respond clinically to EGFR-inhibitor agents.

Mutations of which of the following genes are common in heritable pulmonary arterial hypertension?

• A. Toll-like receptor (TLR).

• B. Bone morphogenetic protein receptor II (BMPR2).

• C. Protease inhibitor (PI ).

• D. Epidermal growth factor receptor (EGFR).

Case No. 6

• A 33-year-old man with longstanding cystic fibrosis was admitted to the ICU 2 days ago with massive hemoptysis for which he was endotracheally intubated and placed on ventilatory support. Chest CT scan revealed bronchiectasis in both lungs but focal air fluid levels and extensive bronchiectasis in the left lower lobe. Flexible bronchoscopy revealed active hemorrhage from the left lower lobe without visible mucosal lesions. He underwent bronchial arteriography with embolization of four suspicious tortuous vessels.

• He has had no recurrence of hemoptysis for the past 48 h, during which time he has remained sedated and paralyzed pharmacologically. Several hours after cessation of neuromuscular blockade, he coughed vigorously and now has recurrent massive hemoptysis with fresh blood filling the endotracheal (ET) tube and ventilator tubing. Despite placing the patient with his left side down and performing aggressive tracheal suctioning, his oxygen saturation by pulse oximetry has rapidly fallen to 70% (with a good waveform) while bag-ventilated with 100% oxygen, and his heart rate is slowing.

Which of the following interventions should be performed next?

• A. Rapid transfusion of packed RBCs.

• B. Flexible bronchoscopy with epinephrine irrigation of bleeding site(s).

• C. Right mainstem bronchus intubation.

• D. Emergent arteriography and repeat embolization.

• Massive hemoptysis is an immediately life-threatening condition, and this patient has evidence of ongoing hemorrhage with flooding of the airway resulting in profound hypoxemia with impending asphyxiation. Urgent isolation of the bleeding lung units from functioning lung units that can support gas exchange is the immediate priority. Blindly advancing the ET tube into the right mainstem bronchus is the most immediately available option because it is highly likely that the bleeding is again from the left lower lobe, and the vast majority of blind bronchial intubations are right sided.

• Urgent flexible bronchoscopy through the advanced ET tube should follow to confirm satisfactory placement, assist in evacuation of blood, and exclude unexpected right-sided bleeding. Careful repositioning of the ET tube such that aeration of the right upper lobe is possible should be considered. Other methods of isolation of bleeding lung units from functional lung include bronchoscopically-guided placement of a catheter with an inflatable cuff , such as a bronchial blocker or Fogarty balloon catheter, which can occlude the bronchus to the active bleeding site. Double-lumen ET tubes are effective at protecting the nonbleeding lung but are difficult to insert properly and limit ability to perform bronchoscopy or suction effectively.

• Hemorrhage-related life-threatening hypoxemia must be corrected as a priority over other interventions. However, subsequently, bronchoscopy may be useful to identify bleeding site(s), clear airway blood, perform balloon tamponade, and provide topical interventions to reduce active bleeding, such as application

• of epinephrine or thrombin, iced saline lavage, or electrocautery. Bronchial arteriography and embolization of suspect bronchial arteries is eff ective at stopping active bleeding in most cases, but recurrence is common. Surgical resection of lung with a localized bleeding site can be defi nitive for persistent or recurrent bleeding. Surgery that is emergent, however, is associated with higher rates of complications and mortality. Diff use underlying lung disease, such as cystic fi brosis, creates added concerns for subsequent recurrent bleeding from a new site after lung resection. Additional general measures include correction of abnormalities in coagulation and platelet number or function, as well as correction of anemia from bleeding.

Which of the following interventions should be performed next?

• A. Rapid transfusion of packed RBCs.

• B. Flexible bronchoscopy with epinephrine irrigation of bleeding site(s).

• C. Right mainstem bronchus intubation.

• D. Emergent arteriography and repeat embolization.

THANK YOU