CHEST自测-点评 (No.50)

此题相应的题目请参阅2007年7月期第443页或 (No.450)的《CHEST自测-题目》。

E. Culture of skin lesions.

This patient has wound botulism, a neuroparalytic illness resulting from the action of a toxin produced by Clostridium botulinum. The toxin causes paralysis by presynaptic blockade of acetylcholine release in skeletal muscle. Signs and symptoms of ocular and bulbar dysfunction are diagnostic clues. Although botulism is best known to be acquired by ingestion of preserved food containing preformed toxin, a similar syndrome may occur when the organism is inoculated into a wound or other devitalized tissue. A dramatic increase in reported cases of wound botulism was linked to subcutaneous or intramuscular injection of 揵lack tar heroin in California. Patients with botulism are typically afebrile, with symmetric weakness, normal level of consciousness, show or normal heart rate in the absence of hypotension, and absence of sensory deficits. The diagnosis of botulism is established by identifying the toxin in the serum, stool, or wound, or the organism in stool or wound cultures. Early cases are more likely to be diagnosed by toxin assay and later cases by culture. Treatment includes wound care, botulinum antitoxin, and supportive care. Injection drug users are also predisposed to developing tetanus by a similar mechanism:when the anaerobe Clostridium tetani colonizes devitalized tissue, an exotoxin disseminates to inhibitory motor neurons, causing paralysis. Unlike botulism, tetanus causes spastic rather than flaccid paralysis. Other progressive neurologic disorders can be excluded base on the clinical presentation.Unlike botulism, acute inflammatory polyneuropathy (AIPN; Guillan-Barr syndrome) frequently begins with sensory complaints, and rarely with cranial nerve dysfunction. The Miller Fisher variant of AIPN may have prominent cranial nerve dysfunction, but also includes ataxia, which is absent in botulism. Tick paralysis can be excluded by the absence of the tick on careful physical examination.

Passaro DL,et al.JAMA 1998;279:859-863

Townes JM,et al.Ann Intern Med 1996;125:558-563

Cherington M.Muscle Nerve 1998;21:701-710

Schaffer N,et al.West J Med 1990;153:390-393


CHEST自测-点评 (No.49)

此题相应的题目请参阅 (No.49)的《CHEST 自测-题目》。

B. Puncture of the thyroid isthmus occurs in less than 5% of properly performed PDT.

Percutaneous dilational tracheostomy (PDT) is now widely performed as a bedside procedure in the ICU. The most widely used technique includes a 1.5cm skin incision over the first tracheal ring, blunt dissection to the pretracheal fascia, and needle puncture of the anterior wall of the tracheal between the first and second or second and third tracheal rings. A guidewire is placed through the needle. After removal of the needle, a tapered curved dilator is inserted over the guidewire to widen the tracheal stoma. The dilator is removed and the tracheostomy tube and obturator is inserted over the guidewire. The procedure is typically performed with deep sedation and ongoing mechanical ventilation through the endotracheal tube that has been retracted over a videobronchoscope to the level of the vocal cords. Videobronchoscopy allows direct visualization of the airway, thereby reducing the risk of posterior tracheal wall trauma or paratracheal tube placement.

Although puncture of the thyroid isthmus is estimated to occur in one third of properly performed PDT, significant bleeding is less common with PDT compared to open tracheostomy. Further,several randomized trials and a recent meta-analysis demonstrate lower complication rates for PDT, particularly for delayed or postprocedural complications such as delayed stomal healing, subglottic stenosis, cosmetic deformities, accidental decannulation, bleeding, and stomal infection. One explanation for these results is that less tissue devitalization occurs with PDT. The blunt force of dilational tracheostomy and presence of the tracheostomy tube does produce tracheal ring damage, however.In an antopsy study, it was demonstrated that PDT causes tracheal ring fracture in most patients and tracheal ring destruction is common if cannulation exceeds 10 days.

Dexter TJ. Anaesthesia 1995;50:863-864

Friedman Y,et al.Chest 1996;110:48-483

Hazard P,et al.Crit Care Med 1991;19:1018-1024

Van Heurn LW,et al.Chest 1996;109:1466-1469

Stoeckli SJ,et al.Laryngoscope 1997;107:1643-1646

DeBoisblanc BP. Percutaneous dilational tracheostomy. In:Shure D,ed. Pulmonary Perspectives.Northbrook IL: American College of Chest Physicians. 2001;18:1-5

Freeman BD,et al.Chest 2000;118:1412-1418





E. Diagnosis using a combination of chest radiography,ventilation-perfusion,and helical CT scanning of the chest with shielding,confers no significant risk of fetal injury.

Physicians are often reluctant to perform radiologic studies during pregnancy because of concern about the effects of radiation on fetal development. However,with appropriate shielding,ventilation-perfusion scanning,pulmonary angiography,and helical CT scanning can all be performed with levels of fetal radiation exposure well below those associated with teratogenicity. For example, a common diagnostic approach for suspected pulmonary thromboembolism (PTE) might include a combination of chest radiography,ventilation-perfusion scanning,and perhaps even a helical CT scan. If all three tests are used in the same patient,the total fetal dose of radiation is generally less than 500 mrad (5 000 u Gy),well below the level of 5 000 mrad (50 000 u Gy) that has been used without significant risk of fetal injury in most studies (thus,choice E is correct).

The risk of venous thromboembolism is five times higher in a pregnant woman than in a non-pregnant woman of similar age,with increased venous stasis being the most constant predisposing factor.In addition to the pressure of the gravid uterus on the venous system of the lower extremities,pregnancy is also associated with elevated levels of coagulation factors II,VII,and X, as well as increased generation of fibrin,all contributing to a hypercoagulable state. During pregnancy,thrombosis most frequently begins in the veins of the calf,or in the ileofemoral segment of the deep venous system and has a significant predilection for the left leg (thus,choice C is incorrect). While the vast majority of deep venous thromboses(DVT) occur ante-partum,it appears that most significant PTE occur during the post-partum period (thus,choices A and B are incorrect).

Investigation of suspected thromboembolic disease in a pregnant patient should follow a similar approach to that in the non-pregnant patient.The ability to diagnose DVT clinically is generally poor and is further hampered durging pregnancy because of the common occurrence of swelling and discomfort of the patient’s legs.Noninvasive tests for lower extremity thrombosis,such as impedance plethysmography and duplex ultrasonography, are considered the initial tests of choice, but because of compression of the iliac veins and vena cava by the gravid uterus, false positive results may occur (thus,choice D is incorrect). The sensitivity and specificity of these noninvasive tests for DVT in pregnancy may be improved if they are performed with the patient in the left lateral decubitus position. It does appear,however,that anticoagulation may be safely withheld if serial noninvasive studies are done and are negative. In order to economize on time in the diagnosis of DVT and PTE,some centers perform helical CT scanning of the chest and CT venography of the legs at one sitting.

Toglia MR,et al.N Eng J Med 1996;335:108-114

Bergqvist A,et al.Acta Obstet Gynecol Scand 1993;62:443-448

Hull RD,et al.Ann Intern Med 1990;112:663-667

Ginsberg JS,et al.Thromb Haemost 1989;61:189-196

Winer-Muram HT,et al.Radiology 2002;224:487-492

Loud PA,et al.AJR Am J Roentgenol 2000;174:61-65




E.Peripheral vascular disease.

The combination of decreased exercise capacity (low Vo2), available cardiac and ventilatory reserve, normal ECG, and very early anaerobic threshold with metabolic acidosis, is best explained by peripheral vacular disease. This patient had severe atherosclerosis supported by the weak peripheral pulses. Although the patient has obstructive airways disease, the achieved peak VE was below the calculated maximal voluntary ventilation. This, coupled with the improvement in arterial blood gas measurements with exercise,rules out ventilatory limitation. Cardiac limitation is characterized by early peak heart rate at submaximal exercise capacity, a drop in blood pressure, and/or development of chest pain or ECG change, none of which were observed in this patient. A submaximal exercise test is also characterized by a low exercise capacity, large ventilatory and cardiac reserve but not with an early anaerobic threshold and the degree of metabolic acidosis seen in this patient. If the problem were deconditioning the peak heart rate should have been reached early and the anaerobic threshold should have occurred at least above 40% of the predicted oxygen uptake.

Tjahja I,et al. Clin Chest Med 1994;15:271285

Levander-Lindgren M,et al.Acta Med Scand 1962;172:678683

Jones N. Clinical exercise testing.Philadelphia: WB Saunders Co;1997



CHEST自测-点评 (No.46)



Noninvasive ventilation (NIV) can deliver respiratory support without the use of an endotracheal tube. It has become an important tool in the armamentarium of ICU and emergency medicine physicians in recent years. Its most resounding success occurs in the type of patient presented in this question: one with a COPD exacerbation. In this setting, it should be used when the patient exhibits moderate respiratory distress with an increased respiratory rate (>24/min), accessory muscle use or paradoxical breathing pattern, and impaired gas exchange (PCO2>45mmHg, PO2/FIO2<200). There are few relative contraindications to use of NIV:

Medical instability (hypotension, arrhythmias, ongoing cardiac ischemia)

Inability to protect the airway, frequent emesis

Severe agitation or uncooperative behavior

Unable to fit or wear the mask

Recent upper airway or gastrointestinal surgery

Although a prior pneumothorax might suggest that caution should be used in initiation of any form of positive pressure ventilation, it would not contraindicate its use (choice C). Regarding the level of acidosis, NIV has been successfully used in this setting, even in the face of significant respiratory acidosis (choice E).

NIV use during COPD exacerbations has been shown in five randomized controlled trials to acutely reverse respiratory acidosis and hypoxemia, decrease the need for intubation, improve mortality and morbidity, and shorten both ICU and hospital length of stays. In the acute setting, a full face mask is typically used rather than the more standard nasal mask that is used to treat patients with obstructive sleep apnea. This is done to prevent mouth leaks that diminish the effectiveness of NIV. This type of mask also works in patients who may have significant nasal obstructive (choice B).

The noninvasive ventilator is usually set up in a pressure format, similar to the mechanical ventilation mode of pressure support. The inspiratory pressure is typically started around 10 to 12 cm of H20 and titrated up or down to attain patient comfort and tidal volume/minute ventilation desired to improve the PCO2. The expiratory pressure (CPAP or PEEP) is typically intiated at around 5 cm of H2O and titrated up, if necessary, to improve oxygenation. It is not recommended that the expiratory pressure go below 4 cm of H2O with most bilevel noninvasive ventilators, as this may cause CO2 buildup.

A living will is an advanced directive in which a patient can itemize what they want done in the event that they have a terminal condition and are no longer competent to make decisions for themselves. The presence of living will is not a contraindication to use of any specific treatment, including mechanical ventilation. The aggressiveness of treatment in the case of a patient with a living will should be decided by the patient and his surrogates. Use of NIV in a patient who has a “Do-Not-Intubate” order or who states such a request in a living will is an ethical gray area. Again, the use of NIV should be frankly discussed with the patient and the surrogates, as uncontrolled series have shown as high as a 60% success rate in this situation.


CHEST自测-点评 (No.45)


D.Pathologic diagnosis is required.

This patient has developed chronic rejection. Bronchiolitis obliterans (BO) is thought to be the sine que non of chronic rejection in the lung transplant (LT) recipient. BO develops in up to 50% of patients following LT, is the leading cause of death after the first year posttransplant, and is the rate-limiting factor for prolonged survival following LT. Typically, BO develops at 16 to 20 months following transplantation, but has been reported as early as 3 months following transplantation. Patients typically present with nonspecific URI-like symptoms or patients may be asymptomatic with deterioration in pulmonary function alone. The chest radiograph is typically unchanged from baseline or may show some hyperinflation. High-resolution CT scans may show bronchiectasis and air-trapping on end-expiratory CT scans. Physiologically, patients demonstrate obstructive dysfunction on their pulmonary function testing.

Numerous risk factors have been postulated to contribute to the development of chronic rejection including acute rejection, CMV pneumonia, CMV infection, lymphocytic bronchiolitis, HLA mismatching, and gastroesophageal reflux disease, several of which were present in this patient's history. However, the most consistently identified risk factor remains acute rejection,particularly when acute rejection is recurrent and/or persistent. Treatment includes augmented immunosuppression with notoriously poor results.

The pathology of chronic rejection is a constrictive bronchiolitis;however, the sensitivity for obtaining the affected terminal bronchioles on transbronchial bronchoscopy is quite variable with most studies reporting yiels as low as 15%. Because of this, the term bronchiolitis obliterans syndrome (BOS) has been used to define this presentation based on the deterioration in FEV1 with or without confirmatory histology, although a bronchoscopy should be performed to exclude alternative diagnoses such as acute rejection and infection. The BOS staging system is shown in Table 1. Currently, this staging system in under revision to identify an earlier stage of BOS called potential BOS based on changes in FEV1 (81% to 90% of baseline) and midflows (FEF25%-75%≤75% of baseline).

Table 1.Clinical Staging for Obliterative Bronchiolitis*

Stage FEV1

0 No significant OB ≥80% of baseline

1 Mild OB 66 to 80% of baseline

2 Moderate OB 51 to 65% of baseline

3 Severe OB ≤50% of baseline

Adapted from Cooper JD, Billingham M, Egan T,et al.A working formulation for the standardization of nomenclature and for clinical staging of chronic dysfunction in lung allografts. J Heart Lung Transplant 1993;12:713-716

*Each stage is subdivided into a and b, where a is without histologic documentation of OB and b is with histologic documentation of OB.


CHEST自测-点评 (No.44)


E.Culture of Aspergillus from respiratory secretions.

Allergic bronchopulmonary aspergillosis (ABPA) is a syndrome characterized by hypersensitivity reaction to bronchial colonization by fungi in the Aspergillus family that typically occurs in patients with asthma.Repeated episodes of airway inflammation and mucoid impaction can result in bronchiectasis,fibrosis,and respiratory insufficiency.A diagnosis of ABPA is made using a combination of clinical,radiologic,and laboratory criteria.While there is no uniformly accepted set of criteria for diagnosis ABPA,there are features that are consistently listed by experts that include: (1)a history of asthma; (2)immediate skin test reactivity to Aspergillus antigens; (3)precipitating serum antibodies to Aspergillus fumigatus; (4)total serum IgE greater than 1 000ng/mL; (5)peripheral blood eosinophilia greater than 500/mm3(>0.5×109/L); (6)recurrent pulmonary infiltrates; (7)proximal bronchiectasis; and(8)elevated specific serum IgE and IgG to Aspergillus fumigatus.Further, a group of experts established criteria for strictly defined ABPA for enrollment of patients into a recent clinical trial that included all of the above noted criteria,except peripheral blood eosinophilia and proximal bronchiectasis.While it is common for patients with ABPA to have sputum or respiratory secretions from which Aspergillus is cultured or visualized by microscopy,the lack of specificity relegates these findings to being suggestive but not diagnostic for ABPA.It is worth noting that ABPA has also been recognized in patients who have cystic fibrosis.


CHEST自测-点评 (No.43)


B. Lateral chest radiograph.

In this case a lateral chest radiograph confirmed multiple compression fractures of the vertebral spine. These fractures explain the remarkable findings on serial spirometry that were small changes in FEV1 and FVC when expressed as percent predicted and large decreases in the absolute values for both FEV1 and FVC. The FVC fell from 3.88 L to 2.90 L, but remained at greater than 80% predicted. Also documented was an accelerated loss of height. Height loss in an older individual is invariably due to vertebral osteoporosis and compression fractures. The restrictive ventilatory defect caused by vertebral compression fractures explains this patient's progressive dyspnea.

Osteoporosis is less common in men than women, but is increasingly being recognized in men as a complication of COPD. In a large randomized, controlled prospective study of the value of inhaled corticosteroids in COPD, 653 patients who had not been receiving inhaled corticosteroids had radiographs of the spine taken at baseline and 81 (12%) were found to have vertebral fractures. In a cross-sectional study of 117 patients with COPD who had not used either inhaled or oral corticosteroids, 48.7% were found to have vertebral Fractures on standard lateral radiographs of the spine. The higher rate of fractures in the cross-sectional study is explained by patient selection. The prospective study enrolled mostly men in their early 50s with approximately a 40 pack-year smoking history. The cross-sectional study included only men in their late 60s with about a 65 to 70 pack-year smoking history. These findings suggest that the prevalence of vertebral fractures in men with COPD will increase with age and smoking history. This patient was in his late 60s and had a greater than 80 pack-year smoking history, putting him at very high risk for osteoporosis and vertebral Fractures. Vertebral fractures are associated with a restrictive ventilatory defect. In an older person with accelerated height loss and a reduction in FVC, the restrictive ventilatory defect can be more clearly seen when arm span rather than height is used for predicting FVC.

The diagnosis of chronic bronchitis is established on the basis of the smoking history and chronic cough. Spirometry confirms obstructive airway disease. According to the GOLD criteria, this patient would be classified as having moderate (stage IIa) COPD. However, the clinical course does not suggest an exacerbation of chronic bronchitis as an explanation for the increasing dyspnea on exertion. A trial of oral corticosteroids would not have been expected to either improve lung function or reduce this patient's dyspnea but would have accelerated bone loss and worsened the osteoporosis. Interstitial lung disease and pulmonary emboli might explain the increased symptoms of dyspnea on exertion without change in cough or wheeze, but would not explain the spirometry findings.


CHEST自测-点评 (No.42)

此题相应的题目请参阅本期第683页的《CHEST 自测-题目》。

D. Change the current ceftriaxone therapy to piperacillin / tazobactam.

The correct answer is option D. This patient with hemoglobin sickle cell disease is presenting with a painful crisis, and may already have some bone marrow suppression. These findings usually precede a fulminant episode of the acute chest syndrome in patients with sickle cell hemoglobin diseases. The usual progression of extremity pain (especially in adults) is to the development of the full-blown acute chest syndrome.

In a recent multi-center study, the etiology of the acute chest syndrome was investigated in a large group of patients.

A specific cause for the syndrome was recognized in 38% of the patients. Infection, usually in the lungs, was the most common recognizable event. Interestingly, the most common etiologic agents were Chlamydia pneumoniae and Mycoplasma pneumoniae, and not Streptococcus pneumoniae. Thus -lactam therapy alone would clearly not be acceptable (option D). Blood transfusions (option A) and supplemental oxygen (option C) are well recognized and time-honored forms of treatment. In a sizeable number of patients, bronchodilator therapy has also been shown to be helpful (option B) because of the coexistence of bronchial hyperresponsiveness.

Therapy directed at community acquired infections in acute chest syndrome must now include treatment that is effective against C pneumoniae and M pneumoniae (option E).


CHEST自测-点评 (No.41)


B. Lateral chest radiograph.

In this case a lateral chest radiograph confirmed multiple compression fractures of the vertebral spine. These fractures explain the remarkable findings on serial spirometry that were small changes in FEV1 and FVC when expressed as percent predicted and large decreases in the absolute values for both FEV1 and FVC. The FVC fell from 3.88 L to 2.90 L, but remained at greater than 80% predicted. Also documented was an accelerated loss of height. Height loss in an older individual is invariably due to vertebral osteoporosis and compression fractures. The restrictive ventilatory defect caused by vertebral compression fractures explains this patient's progressive dyspnea.

Osteoporosis is less common in men than women, but is increasingly being recognized in men as a complication of COPD. In a large randomized, controlled prospective study of the value of inhaled corticosteroids in COPD, 653 patients who had not been receiving inhaled corticosteroids had radiographs of the spine taken at baseline and 81 (12%) were found to have vertebral fractures. In a cross-sectional study of 117 patients with COPD who had not used either inhaled or oral corticosteroids, 48.7% were found to have vertebral Fractures on standard lateral radiographs of the spine. The higher rate of fractures in the cross-sectional study is explained by patient selection. The prospective study enrolled mostly men in their early 50s with approximately a 40 pack-year smoking history. The cross-sectional study included only men in their late 60s with about a 65 to 70 pack-year smoking history. These findings suggest that the prevalence of vertebral fractures in men with COPD will increase with age and smoking history. This patient was in his late 60s and had a greater than 80 pack-year smoking history, putting him at very high risk for osteoporosis and vertebral Fractures. Vertebral fractures are associated with a restrictive ventilatory defect. In an older person with accelerated height loss and a reduction in FVC, the restrictive ventilatory defect can be more clearly seen when arm span rather than height is used for predicting FVC.

The diagnosis of chronic bronchitis is established on the basis of the smoking history and chronic cough. Spirometry confirms obstructive airway disease. According to the GOLD criteria, this patient would be classified as having moderate (stage IIa) COPD. However, the clinical course does not suggest an exacerbation of chronic bronchitis as an explanation for the increasing dyspnea on exertion. A trial of oral corticosteroids would not have been expected to either improve lung function or reduce this patient's dyspnea but would have accelerated bone loss and worsened the osteoporosis. Interstitial lung disease and pulmonary emboli might explain the increased symptoms of dyspnea on exertion without change in cough or wheeze, but would not explain the spirometry findings.


CHEST自测-点评 (No.40)


C. A kidney biopsy.

This patient has a pulmonary-renal syndrome, the differential diagnosis of which includes Goodpasture's syndrome and Wegener's granulomatosis, among others. Most patients with the pulmonary-renal syndrome ultimately receive systemic corticosteroids and cytoxan. In patients with Goodpasture's syndrome, however, plasmapheresis should be rapidly instituted in an attempt to prevent progression to end-stage renal disease and the resulting need for chronic dialysis. This may be particularly important in patients like the one described, who have only a modest elevation in creatinine. This implies that fewer glomeruli are destroyed, and the possibility of needing chronic dialysis is reduced.When the serum creatinine level at admission exceeds 5 mg / dL (442 u mol / L), the opposite is true. Plasmapheresis is also routinely employed for patients with hemoptysis, as this can be a fatal complication.

Accordingly, the objective in patients with the pulmonary-renal syndrome is to establish the diagnosis quickly. Indirect immunofiuorescence is performed by incubating the patient's serum with normal renal tissue and subsequently adding fluorescein-labeled anti-human IgG to see if the patient's antiglomerular basement membrane antibody (an IgG directed against the NC 1 domain on the α-3 chain of type IV collagen) is deposited on the normal kidney. Although this test can be done in only a few hours and is diagnostic if positive, the false-negative rate is approximately 40%. The negative result in the patient presented does not, therefore, exclude the diagnosis of Goodpasture's syndrome.A direct enzyme-linked immunosorbent assay (ELISA) seeking circulating antiglomerular basement membrane antibodies in the serum is a much more sensitive and specific test. Although it can be done in a few hours, the test is not routinely available, and it generally takes several days to obtain a result. In addition, questions have been raised about the extent to which the antigen used by some commercial laboratories is purified, as false-positive results have been reported.

Processing of renal tissue can be accomplished rapidly (generally the same day) and, accordingly, a kidney biopsy should be performed if the indirect immunofluorescent antibody test is negative. Although crescentic glomerulonephritis is a nonspecific finding, linear IgG deposition along the glomerular capillaries is diagnostic in this clinical setting.

Lung biopsies can also show the typical immunofluorescent staining pattern, but the additional prognostic information gleaned by determining the extent of glomerular involvement makes the kidney the preferential organ for a biopsy.

Blood should also be sent for an antineutrophil cytoplasmic antibody (ANCA) test. A positive result does not exclude Goodpasture's syndrome, however, as up to 38% of patients with antiglomerular basement membrane antibodies will also have positive p-ANCAs in the setting of a systemic vasculitis, and in these, plasmapheresis would still be indicated.


CHEST 自测-点评 (No.39)

此题相应的题目请参阅No.39的《CHEST 自测-题目》。

B. Hydrostatic pulmonary edema due to volume overload.

The specific pulmonary artery occlusion pressure (PAOP) that one selects as a determinant of "high pressure" vs "low pressure" pulmonary edema is arbitrary because degrees of lung injury, hypoalbuminemia, volume overload,and ventricular dysfunction may all promote lung flooding. The expected PAOP threshold for hydrostatic edema,assuming normal permeability and Starling forces, is approximately 22 to 25 mm Hg. The significance of an isolated reading is hard to interpret, especially when recorded after a therapeutic intervention (intubation, sedation, elevated FIO2, vasodilator administration, etc). Furthermore, the PAOP represents the lowest average pressure across the vascular bed with 18 mm Hg being the threshold listed in the literature above which concern for upstream hydrostatic edema is entertained. When pulmonary artery and venous resistances are normally distributed, the pulmonary capillary pressure (Pcp), which is the pertinent upstream pressure driving fluid flux into the alveolar space, can be closely approximated by the Gaar equation:

Pcp = PAOP + 0.4 (Ppam - PAOP)

Ppam represents the mean pulmonary artery pressure. Actual Pcp is affected by increases in PAOP, pulmonary blood flow, pulmonary arterial pressure, or venous resistance (Rv). Rv is increased in sepsis, ARDS, following PEEP,and after the administration of certain pharmacologic agents. New methods of clinically calculating Pcp have been introduced which examine the exponential decay of the pulmonary artery pressure waveform during balloon occlusion.

Using the Gaar equation, this patient's pulmonary capillary pressure is calculated to be 26.6 mm Hg, clearly above the pressure needed to produce hydrostatic leak and most likely explaining the patient's clinical picture of pulmonary edema. The hemodynamic profile of low systemic vascular resistance and increased cardiac output that resembles sepsis is, in fact, due to changes seen with fluid overload and in this case concurrent antihypertensive vasodilator therapy.

The patient's clinical presentation to the ICU with rapid onset pulmonary edema, normal temperature and WBC count do not strongly support sepsis but cannot exclude sepsis as a factor in the patient's respiratory failure. There was no history of aspiration or administration of a toxic pulmonary drug. Further dialysis cleared this patient's pulmonary edema and allowed for extubation in 24 hours consistent with the diagnosis of hydrostatic pulmonary edema.



CHEST 自测-点评 (No.38)

此题相应的题目请参阅No.38的《CHEST 自测-题目》。

D. Rate of decline of lung function.

Three randomized, double-blind, placebo-controlled clinical trials (grade I studies) lasting over 6 months to 3 years have shown that inhaled corticosteroids provide significant improvements in patients with moderate to severe COPD in all of the outcomes listed EXCEPT slowing down the rate of decline in lung function (choice D). In addition to improving respiratory symptoms (choice A), decreasing the rate of exacerbations by 25% per year (choice B),increasing 6 minute walking distance (choice C), and slowing the rate of decline in health-related quality of life from 15 to 24 months (choice E), inhaled corticosteroids have also significantly decreased the severity of exacerbations and the use of health-care services (emergency department visits, unscheduled physician office visits, and COPD-related hospitalizations) for respiratory symptoms. In these studies, the doses of inhaled corticosteroids were 1200ug/d of triamcinolone or 1000ug/d of fluticasone.

While similar doses of inhaled corticosteroids have been inconsistently shown to slow down the rate of decline of lung function for short periods of time (eg, 6 months or less), they have not been able to do so for longer periods of time (choice D). While some grade I studies have demonstrated that inhaled beclomethasone in a dose of 1 000ug/d has an anti-inflammatory benefit as reflected by significant falls in exhaled nitric oxide that correlated (P = 0.02) with increases in FEV1, others have failed to show such an effect on sputum inflammatory indices, cytokines, or proteases with fluticasone in a dose of 1 000ug/d.

Based on multiple studies, inhaled corticosteroids in patients with moderate to severe COPD have led to long-term improvement in 7 of 9 outcomes. On the other hand, compared to placebo, grade I studies in COPD patients have inconsistently shown that long-term inhaled corticosteroid use leads to more skin bruising, bone loss, oropharyngeal candidiasis, throat irritation, and lower serum cortisol levels. Compared to placebo, these studies have not shown more hypertension, bone fractures, postcapsular cataracts, myopathy, diabetes, or dropouts.


CHEST 自测-点评 (No.37)

此题相应的题目请参阅No.37的《CHEST 自测-题目》。

D. Obesity.

Despite a common assumption that obesity increases the risk of pulmonary complicaticms, most studies have found no such association. Cigarette smoking is a risk factor with a relative risk ranging from 1.4 to 4.3. This risk declines only after 8 weeks of smoking cessation. Poor general health status is a strong predictor of complications. Both the Goldman cardiac-risk index and the American Society of Anesthesiologists (ASA) classification are predictive of pulmonary complications. The Goldman cardiac-risk index includes factors from the patient's history, the physical examination, and laboratory data. This index predicts pulmonary as well as cardiac complications. The widely used ASA classification, which was developed to evaluate the risk of overall perioperative mortality, is also strongly predictive of postoperative pulmonary complications. The ASA classification system is based on the presence or absence of systemic disturbances: absent (class 1), mild (class 2), moderate (class 3), severe (class 4), or almost certain death (class 5).

Studies suggesting an increased risk of pulmonary complications with older age have not generally controlled for coexisting conditions. Although age > 70 can be statistically identified as a risk factor, puhnonary complications are more strongly related to coexisting conditions than to chronologic age, and therefore advanced age alone is not a reason to withhold surgery. COPD is a strong predictor of complications. Patients with COPD carry a relative risk of complications ranging from 2.7 to 4.7.



CHEST 自测-点评 (No.36)

此题相应的题目请参阅No.36的《CHEST 自测-题目》。

E. Start liposomal amphotericin B at 6 mg/kg/d.

The correct answer is to administer liposomal amphotericin B (LAMB) at 6 mg/kg/d (choice E). Neutropenic fever may be treated empirically for fungi if the patient remains febrile after 3 to 5 days of standard broad spectrum antibiotic therapy. Although many agents have been used, at the present time the accepted and approved agent is amphotericin B deoxycholate (AMB) when aspergillosis is suspected. The reason aspergillosis is suspected in this patient is because the fever persisted after 2 days offluconazole therapy. Because the patient's creatinine is elevated,LAMB should be used in preference to AMB to reduce the likelihood of further renal damage.

Although two new agents have been introduced (voriconazole and caspofungin), neither agent has documented superiority to LAMB. In a recent article, voriconazole performed almost as well as LAMB, but the composite end point did not reach equivalence. Caspofungin was also shown to be effective, but no carefully done randomized controlled trial has been published comparing caspofungin to LAMB. While aspergillosis remains the most common fungal infection (after candidiasis), other mold infections may also occur.

Because the patient still has a clear chest radiograph and the results of the BAL from 2 days ago shows no pathogens, repeat bronchoscopy and BAL is not indicated (choice A). Changing antibacterial antibiotics is not likely to add anything, because there are no organisms to target (choice B). While oral itraconazole has been used in this setting, it is inferior to LAMB (choice C).

Although an additive effect is not yet proven, increasingly clinicians are using combinations of LAMB and caspofungin. While this combination makes sense (the agents have different molecular targets), at the present time this should be considered experimental therapy.


CHEST 自测-点评 (No.35)

此题相应的题目请参阅No.35的《CHEST 自测-题目》。

D. Obesity.

Despite a common assumption that obesity increases the risk of pulmonary complicaticms, most studies have found no such association. Cigarette smoking is a risk factor with a relative risk ranging from 1.4 to 4.3. This risk declines only after 8 weeks of smoking cessation. Poor general health status is a strong predictor of complications. Both the Goldman cardiac-risk index and the American Society of Anesthesiologists (ASA) classification are predictive of pulmonary complications. The Goldman cardiac-risk index includes factors from the patient's history, the physical examination, and laboratory data. This index predicts pulmonary as well as cardiac complications. The widely used ASA classification, which was developed to evaluate the risk of overall perioperative mortality, is also strongly predictive of postoperative pulmonary complications. The ASA classification system is based on the presence or absence of systemic disturbances: absent (class 1), mild (class 2), moderate (class 3), severe (class 4), or almost certain death (class 5).

Studies suggesting an increased risk of pulmonary complications with older age have not generally controlled for coexisting conditions. Although age > 70 can be statistically identified as a risk factor, puhnonary complications are more strongly related to coexisting conditions than to chronologic age, and therefore advanced age alone is not a reason to withhold surgery. COPD is a strong predictor of complications. Patients with COPD carry a relative risk of complications ranging from 2.7 to 4.7.


CHEST 自测-点评 (No.34)

此题相应的题目请参阅No.34的《CHEST 自测-题目》。

B. Anti-topoisomerase 1 (SCL-70).

The patient has progressive dyspnea and near syncope, with a palpable and audibly accentuated P2 on auscultation (suggesting pulmonary hypertension). These findings are accompanied by basal crackles with roentgenographic evidence of interstitial lung disease and periungual telangiectasias. Importantly, there are also symptoms of esophageal reflux and symptomatic Raynaud's phenomenon; the patient has also developed progressive renal failure requiring dialysis. This constellation of historical features, symptoms, and current findings is strongly suggestive of progressive systemic sclerosis (scleroderma). The serum anti-topoisomerase test (also known as SCL-70) is highly specific for progressive systemic sclerosis (PSS). In a recent series, the incidence of false positive results was 0.36% (1 of 264); the test yielded a true positive result in 26% of patients. In this patient the SCL-70 was 1:640, accompanied

by a modestly positive antinuclear antibody. Some patients will present with a limited form of PSS known as CREST (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia), which may be accompanied by pulmonary hypertension (even more commonly than with diffuse disease) and/or interstitial lung disease.

In terms of diagnostic utility, the skin biopsy from non-sun-exposed areas is useful in the evaluation of patients for systemic lupus erythematosus, which is highly unlikely in this patient. In fact, some of the skin changes noted, such as nail pitting, are attributable to the patient's long-standing psoriasis, rather than to the rheumatoid latex agglutination test, which though possibly positive in such a patient, is quite non-specific. Renal biopsy, which might provide useful histologic information, is not indicated in this frail elderly man who already has end-stage renal disease requiring dialytic therapy. The open lung biopsy would not yield specific results; the presence of severe pulmonary hypertension makes transbronchial lung biopsy risky.


CHEST 自测一点评 (No.33)

此题相应的题目请参阅No.33的《CHEST 自测一题目》。

A. Lower extremity exercise improves exercise capacity.

The best answer is A. Pulmonary rehabilitation (PR) involves multidisciplinary programs lasting several weeks that provide exercise, education, medication optimization, and other modalities to improve the functional capabilities of patients with chronic lung disease. In 1997, the American Association of Cardiovascular and Pulmonary Rehabilitation and the American College of Chest Physicians published the conclusions of a task force commissioned to review the evidence base supporting benefit to PR programs. The evidence was graded A (consistent results from controlled trials), B (observational studies or inconsistent results from controlled trials), or C (opinions of experts based on other forms of data).

In this report, grade A evidence supported the use of lower extremity exercise to improve exercise capacity (choice A).Grade A evidence also supported the observation that PR programs reduce dyspnea. Because only grade B evidence supported the benefit of upper extremity exercise, ventilatory muscle training in some patients, and the observations that PR programs reduce hospitalizations and improve HRQL, choices D and E are wrong. Similarly, because only grade C evidence exists supporting the role of formal psychosocial programs or the claim that mortality might be reduced by PR programs, choices B and C are wrong.

Since this evidence-based review was published, additional publications have appeared that further support the concept that formal exercise training produces significant functional improvement in patients with chronic lung disease. These studies suggest that the improved exercise capacity is often due to multiple factors including improved cardiovascular fitness, better dyspnea tolerance, peripheral muscle training, and less fear of exercise.

These data are prompting the willingness of third party payers to cover the costs of PR. Indeed, the NIH-Medicare large randomized trial of lung volume reduction surgery in patients with severe emphysema required PR in all patients pre-randomization.


CHEST自测-点评 (No.32)


C. Daily changes of heat and moisture exchanger.

Ventilator-associated pneumonia (VAP) is a common complication of mechanical ventilation that is accompanied by attributable prolongation of ICU and hospital length of stay,increased cross, and perhaps increased mortality. Various pharmacological and nonpharmacological interventions have been proposed and some have been tested for effectiveness in formal clinical trials. These interventions are generally based on modifying the pathogenesis of ventilator-associated pneumonia, which includes colonization of the aerodigestive tract, aspiration of infected material into the lower respiratory tract, and the failure of host defense mechanisms. Semirecubent positioning (choice A) with consistent elevation of the head of the bed to at least 45 degrees above horizontal was associated with significantly lower VAP rate compared to supine positioning at 0 degrees in a multicenter clinical trial. The use of specially designed endotracheal tubes that permit removal by continuous or intermittent suction of secretions that pool above the endotracheal tube cuff has been associated with lower VAP rates in several single-center, randomized controlled trials (choice B), although clinical use of these tubes is limited. Similarly , delivery of positive pressure ventilation using a face mask rather than a traditional endotracheal tube is accompanied by lower VAP rates in several multicenter clinical trials (choice D). The proposed reasons for lower infection rates among patients treated with mask ventilation include more upright patient positioning, preserved cough reflex and airway reflexs due to less pharmacological sedation, and absence of the endotracheal tube that may act as a conduit through the vocal cords for secretions. Additional measures with documented efficacy in reducing VAP rates include oral decontamination utilizing 0.12% chlorhexidine gluconate oral rinse in cardiac surgery patients, and application of an antibiotic paste to the oral cavity of selected patients. In contrast to these measures, daily changing of heat and moisture exchangers and in-line suction catheters is not associated with reduced VAP rates when compared to less frequent schedules (choice C). Recently the development and implementation of a multidisciplinary education program directed primarily at respiratory therapists and ICU nurses was associated with a three-fold reduction in VAP rates (choice E). Key components of this program include use of orotracheal rather than nasotracheal intubation, use of orogastric rather than nasogastric tubes, elevation of the head of the bed , prevention of unplanned extubation, avoidance of gastric overdistension, provision of oral hygiene, use of mask ventilation when possible , avoidance of overuse of antibiotics, drainage of ventilator condensate in a sterile fashion, and use of influenza and pneumococcal vaccines.




E. The measured DLCO will be reduced by the lung volume reduction but the reduction will be much less than a 1:1 relationship with any measured lung volume.

The best answer is E. As the lung expands from residual volume to total lung capacity, changes in the alveolar capillary membrane and capillary blood volume increase the ability of the lungs to transfer CO and thereby increase the measurement of DLCO. Submaximal inspired volumes (ie, less than the subject's known vital Capacity) would therefore be expected to reduce the measurement of DLCO (thus, choice D is wrong).

Numerous investigations, however, have shown that this reduction in DLCO is much less than a 1:1 relationship with any reduction in lung volume (ie, %DLCO reduction is less than %VA [or TLC or VI] reduction when inspired volume is reduced). Indeed, the empiric formula.

DLCOcorrected = DLCOobserved/(.58 + .42 ?[VAobserved/VAexpected])
fits much better the observed data in normal subjects inspiring to less than the expected VA.

The importance of using this more complex adjustment can be illustrated in a subject with normal spirometry who has a measured DLCO of 64% predicted after a submaximal inspiratory effort that resulted in a 50% predicted VA. The clinical question is whether this reduced DLCO reflects lung pathology or whether it is simply a reflection of the reduced VA. Simple division of the percent predicted DLCO by the percent predicted VA would yield a value of 128% (64%/50%), an implication that the CO uptake properties are supra-normal. However, if the equation in the previous paragraph is used, we find that volume-adjusted DLCO percent predicted is = 64%/(0.58 + 0.42 ?[50%/100%]) =90%. This implies that real CO uptake properties are in the normal range and that the observed reduction in DLCO was due to the reduced VI and VA.

The validity of adjustments for a reduced VI and VA in lung disease where lung pathology has simultaneously reduced both CO uptake properties and VA is not clear. In some of these disease states, the reduction in DLCO is less than the reduction in VA (eg, patients post pneumonectomy often have a high DLCO/VA); in others, the reduction in DLCO is greater than the reduction in VA (eg, patients with pulmonary vascular disease often have a low DLCO/VA). However, in many disease states the relationship of a simultaneous pathologic reduction in DLCO and VA may be quite variable and of unclear physiologic or clinical significance. Under these circumstances, adjustments to the observed DLCO such as those described above should be used with caution.




B. The two largest FVC and FEV1 maneuvers should agree within 0.2L.

Pulmonary function test (PFT) interpretation is a mandatory skill of pulmonologists. There are a variety of PFTs available including spirometry, lung volumes, and diffusing capacity. This testing is typically performed in a pulmonary function laboratory. Because some diagnoses are based on the results of PFTs, it is important for these laboratories to meet certain quality standards in the performance of these tests. The American Thoracic Society (ATS) has published standards for spirometry that have 3 components: equipment, calibration, and testing procedures. This question deals with the latter, testing procedures. All physicians interpreting PFTs should be familiar with the testing standards to ensure that their PFT interpretation is of high quality.

The ATS standards for spirometry (flow-volume loop) state that the two largest FVC and FEV1 maneuvers should agree 0.2 L (choice B is thus correct). The other standards include: a minimum of 3 acceptable trials; a brisk exhalation without hesitation; expiration lasting a minimum of 6 seconds; continuation of exhalation until there is no volume change for 1 second; and the two largest peak expired flow (PEF) measurements should agree within 10%.

Although this question deals with spirometry, it is important to appreciate that there are standards for performing other PFTs, for example, diffusing capacity. The ATS also has such standards for diffusing capacity. These are: the breath hold time must be within 9 and 11 seconds; the inspiratory time must be 2.5 seconds (4 seconds for patients with obstrctive lung disease); the inspiratory volume must be at least 90% of the patient's own best vital capacity; two acceptable trials should be performed and the results should be within 10% of one another or within 3 mL CO/min/mm Hg; and the diffusing capacity should be within physiological limits (20 to 200% predicted).

There are currently no universally agreed upon standards for lung volumes.



A. Similar to the lung, systemic vascular beds vasoconstrict in the face of hypoxemia.

Hypoxemia results in a number of adverse effects to the human body. As the PO2 drops below 55 mm Hg, ventilatory drive rises and PCO2 falls. The pulmonary arteries respond by vasoconstricting, trying to increase ventilation-perfusion matching. However, when tissues become hypoxic, the systemic vascular beds dilate, resulting in tachycardia and increased cardiac output. This improves oxygen delivery.

Other effects of chronic hypoxemia include erythrocytosis secondary to increased erythropoietin production; pulmonary hypertension; malnutrition; impaired judgment, learning, and short-term memory loss; and poor sleep quality. In patients with COPD, the hypotonia that occurs in REM sleep results in loss of the use of the accessory muscles of respiration. This results in a lowering of the functional residual capacity (FRC) and increased ventilation-perfusion mismatch. This phenomenon has been associated with the development of pulmonary hypertension in COPD patients with PO2 levels<60 mm Hg. The neuropsychological deficits noted in chronic hypoxemia have been shown to correlate with the degree of hypoxemia.

Almost 1 million patients in the United States are on supplemental oxygen with a yearly cost slightly less than $2 billion. It has been shown by the Nocturnal Oxygen Therapy Trial study (NOTT) that the use of supplemental oxygen does improve survival, and that longer daily use (> 18 hours per day) was better than only nocturnal use. The current indications for supplemental oxygen include a PO2 < 55 mm Hg (or SaD2 < 88%) or a PO2 of< 59 mm Hg in the presence of cot pulmonale or polycythemia. In relationship to delivering oxygen via nasal cannula, it is known that flow is highest during the early part of inspiration; this is when the majority of oxygen is delivered to the alveoli. Therefore, devices which reservoir or pulse oxygen have been developed to "frontload" oxygen at the beginning of inhalation. This decreases the amount of oxygen used by not delivering it through the entire respiratory cycle.

In addition to improved survival, supplemental oxygen use has been shown to have several favorable physiologic benefits. Pulmonary hypertension improves when oxygen is used as opposed to worsening if hypoxemia is left untreated, however, nocturnal oxygen alone does not appear to decrease pulmonary hypertension significantly. Use of oxygen can also increase exercise endurance and reduce dyspnea.



C. Direct toxic effect of zinc oxide.

The patient suffers from recurrent bouts of metal fume fever. This condition results from the inhalation of minute particles of the oxides of various metals, most commonly zinc. The disorder has also been described, although much less commonly, in workers exposed to the oxides of copper and magnesium. The pathogenetic mechanism is felt to be a direct toxic effect. The syndrome may develop on the first day of exposure thus arguing against an immunologic etiology.

The symptoms of the disease are the sudden onset of thirst and a metallic taste in the mouth. There is usually a 4-to 8-hour lag before these symptoms occur. Later the subject may develop rigors, high fever, myalgia, headache, and weakness. There is profuse sweating. Symptoms subside in 24 to 36 hours.

Metal fume fever is the acute respiratory illness most frequently encountered by welders. Because the most common cause of this acute and self-limiting febrile illness is freshly generated zinc oxide fumes, welders who work on galvanized sheer metal (usually steel coated with zinc) experience metal fume fever unless special precautions are taken to minimize inhalation exposures.

Antimony has been used since ancient times as a cosmetic and as a constituent of bronzes and other alloys. Antimony has many other industrial and medicinal applications. Chronic cough due to respiratory tract irritation may be noted by exposed workers but there have been no reports of symptoms suggestive of metal fume fever. Direct activation of the alternate complement pathway by mycotoxins is one of several proposed mechanisms of the organic dust toxic syndrome (formerly referred to as "mycotoxicosis".



E. Infusions are associated with metabolic acidosis.

Diazepam infusions, not midazolam infusions, can be associated with metabolic acidosis, because the carrier for the parenteral drug is propylene glycol and ethyl alcohol. Therefore, option E is not true, which makes it the correct option.

When midazolam is given as a continuous infusion, midazolam begins to accumulate and acts as a longer acting drug. The duration of the infusion directly influences the pharmacokinetic properties of midazolam. Tolerance occurs quite rapidly with midazolam continuous infusions and withdrawal symptoms can be seen when midazolam infusions are discontinued. Therefore, option D is true.

Two recent clinical investigations have documented that continuous infusions of midazolam lead to prolonged hospitalizations, prolonged mechanical ventilation and more tracheostomies. Therefore, options A, B, and C are true. These investigations suggested that either the sedative be given according to a protocol, so that dosing be decreased based on a protocol, or the infusion be stopped on a daily basis so that the patient would withdraw from the drug and a lower dose could be administered. These investigations did not document an optimal level of sedation, rather the studies determined that continuous infusions oversedate patients, which leads to these undesired outcomes.




D. Hypersensitivity pneumonitis.

All of the listed diseases with the exception of hypersensitivity pneumonitis (HP) have an association with smoking. HP, in fact, may have a lower incidence in smokers. Smoking may have a protective effect in HP and sarcoidosis. In several studies, only 13 to 27% of patients who developed HP were smokers. In HP, cigarette smoking may suppress specific antibody formation, decrease the percentage of T helper lymphocytes, and impair macrophage immune function, important in the pathogenesis of the disease.

The incidence of bronchogenic carcinomas is increased in tobacco users, and tobacco use is the cause of 80 to 90% of lung cancers. The likely pathogenic mechanism is related to damage to the DNA in the cells of the bronchial epithelium. Desquamative interstitial pneumonitis (DIP) is a distinctive form of interstitial lung disease characterized by evenly dispersed pigmented macrophages in alveoli and has a clear association with tobacco use. Over 90% of patients with DIP are smokers. Discontinuation of tobacco use can result in spontaneous resolution of DIP. Eosinophilic granuloma (EG) or Langerhans' cell histiocytosis is most common in male smokers and may respond to discontinuation of tobacco use. Smoking may cause or exacerbate EG by inducing an increase in Langerhans cells in the lungs and/or by inducing accumulation of neuroendocrine cells resulting in an increased secretion of profibrotic and proinflammatory mediators. An alternate hypothesis is that affected patients have an abnormal immune response to tobacco glycoproteins. Goodpasture's syndrome is a pulmonary-renal syndrome affecting young male smokers. Nearly 100% of patients with Goodpasture's disease who develop concomitant pulmonary hemorrhage are smokers. It is thought that tobacco smoke results in mild lung injury allowing increased access of the anti-glomerular basement membrane antibody to the alveolar basement membrane.



E. Failure to receive pneumococcal vaccination.

In a recent large study of nursing home residents, the history of pneumococcal vaccination failed to provide protection form the development of a first episode of pneumonia (choice E).

Because the study did not cover the effect of vaccine on subsequent episodes of pneumonia, it still possible that the pneumococcal vaccine might have some protective effect against invasive pneumococcal disease, but previous prospective studies have clearly shown that the elderly frequently failed to develop adequate antibody titers to the vaccine strains. To this date, the state of pneumococcal vaccination in the elderly is open to question. A conjugate pneumococcal vaccine is currently undergoing clinical trials and it may prove to be effective. In the same study age (by decades), male gender and swallowing difficulty were predictive for the development of the first episode of pneumonia (choices A, C, and D), while having been vaccinated against influenza was protective (choice B).



A. Dead space to tidal volume ratio.

Cardiopulmonary exercise testing is a valuable tool in evaluating the cause of unexplained dyspnea. In planning the test, you need to determine whether it is appropriate to monitor arterial blood gases in addition to the ventilatory, and cardiac measurement variables. Arterial blood gas measurements are required for measuring dead space to tidal volume ratio (Vd/Vt) and the alveolar-arterial oxygen gradient [P(A-a)O2]. Normally, the fraction of each breath going to dead space (Vd/Vt) decreases with exercise from 0.3 to 0.18. This is due to increases in tidal volume and perfusion to the upper lung zones as cardiac output increases. Vd / Vt is calculated by the following formula:

Vd/Vt = PaCO2 -PeCO2 / PaCO2

where PaCO2 is arterial CO2 (mm Hg), and PeCO2 is mid-expired CO2 (mm Hg)(average CO2 partial pressures of expired gas).

An abnormal Vd / Vt response reflects abnormal gas exchange. In patients with pulmonary parenchymal diseases including COPD, Vd / Vt may be elevated at rest and does not decrease normally with exercise. In patients with pulmonary vascular disease, Vd / Vt is elevated at rest and may increase with exercise. However, the Vd / Vt response is normal in obesity and deconditioning. Patients with cardiomyopathy may have mild Vd / Vt abnormalities that worsen as cardiac function declines. Likewise, patients with mitochondrial myopathy have normal resting Vd / Vt that, with exercise, may decrease less than expected because of these patient's inability to reach peak exercise intensity. The other answers can be derived from noninvasive techniques including on-line breath-by-breath analysis of respiratory gas exchange including minute ventilation, tidal volume, respiratory rate, oxygen fraction, and CO2 fraction. Heart rate, ECG, work rate, pulse oximetry, and symptoms are also measured. Oxygen pulse (mL/beat) is the amount of oxygen consumed per heart beat and is a noninvasive surrogate for stroke volume. Ventilatory equivalent for CO2 (Ve/Vco2) is a noninvasive surrogate for Vd / Vt. CO2 output is simply Vco2 (L/min). Peak O2 uptake (L/min) is the maximal amount of oxygen consumed per minute during exhaustive exercise and is used interchangeably with maximum O2 uptake.



B. A 55-year-old man with a 2.5-cm left lower lobe adenocarcinoma with a chest CT scan revealing normal sized mediastinal nodes.

Positron emission tomography (PET) is based on the concept of uptake of substances such as glucose by metabolically active lesions. PET scanning is relatively new to the armamentarium for the staging of non-small cell lung cancer and evaluation of solitary pulmonary nodules (SPN). Typically a fluorine tagged glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) is used. Standard uptake values (SUV) ≥2.5 are considered significant. In several studies, the overall sensitivities and specificities of PET scanning for detection of pulmonary malignancy have been found to be 85 to 100% and 82 to 90% respectively with positive and negative predictive values approaching 87 to 95%. PET scanning appears to be most useful for imaging and staging of the mediastinum and has been found to have sensitivities and specificities of 85% and 88%, respectively. In comparison, CT scanning has a lower sensitivity and specificity for staging of the mediastinum of 60% and 81%, respectively. For the evaluation of a solitary pulmonary nodule (SPN) for malignancy, sensiti-vity and specificity are 95 to 97% and 70 to 78%, respectively, with PET scan. CT evaluation of SPN has sensitivities and specificities of 70 to 80% and 60 to 73%, respectively. In this question, the patient in choice B would be the best candidate to undergo a PET scan. This patient is a non-diabetic with lung cancer and it is important that the mediastinum be staged prior to consideration for resection. The recently published American College of Chest Physicians evidence-based guidelines on lung cancer support performing a PET scan to stage the mediastinum prior to proceeding to surgery in all patients with normal appearing (≤10 mm short-axis diameter) mediastinal nodes on CT scan. This is level B evidence. If the PET scan is suggestive of mediastinal invasion, then surgical investigation is required. If the PET scan is negative, the patient can proceed to surgical resection. The guidelines suggest proceeding directly to mediastinal exploration prior to surgical resection in the event of enlarged (> 10 mm short-axis diameter) nodes on CT scan. This is level B evidence. False positive PET scan results can occur. The most common causes include: solitary pulmonary nodules due to fungal infections (including histoplasmosis and coccidioidomycosis), tuberculosis, sarcoidosis, lung abscesses, and small areas of pneumonia among other. In choice E, the patient has a history of histoplasmosis and there could be concern for false positive results. False negative results can occur in tumors with low metabolic activity, classic examples being bronchoalveolar cell caricinoma and carcinoid tumors. Small lesion size is another cause of false negative PET scan results. The lower limit of resolution for PET scanning for a pulmonary nodule is usally 1 to 1.2 cm. Thus, choice D would be less correct. In Patients with poorly controlled diabetes, the endogenous glucose will compete with FDG-glucose and result in decreased accumulation in malignant tissues. False negative scans can occur, thus choice A would not be the best use of this imaging study. FDG-PET scanning is notoriously poor for imaging the brain where diffuse uptake occurs, and thus is not a useful test when evaluating possible brain metastases as in patient C. Other sites of distant metastases such as the bone, liver, and adrenal glands are usually well assessed by PET. PET scanning has not been found to be useful for staging for contiguity of malignancy in the mediastinum or the chest walll, or direct invasion of the mediastinum by tumor. Both residual thymic structures and active goiters can give false positive results in the mediastinum.


C. Slows the velocity of the aerosol particles.

The best answer is C. Pressurized metered dose inhalers (pMDIs) are effective devices to deliver aerososls into the lower respiratory tract. Advantages over liquid nebulization systems include portability, short treatment times, and reduced costs. Disadvantages include a requirement for good patient-device coordination (ie, the pMDI should be activated early during a slow inspiratory capacity maneuver), the high velocity of the spray (which promotes oropharyngeal deposition), and the cold temperature of the spray (which can cause a premature termination of the patients's inspiratory effort-the "old freon" effect).

A holding chamber of at least 100 mL (available sizes are up to 750 mL) does several important things to improve lung deposition from a pMDI. First, it slows the velocity of the aerosol coming from the opening of a pMDI (choice C). This significantly reduces the oropharyngeal deposition from impaction. Second, chambers allow the pMDI to be discharged into it prior to an inspiration (not mid inspiration, thus choice B is wrong) thereby enhancing effectiveness in patients with hand-inhalation uncoordination. Third, chambers allow propellants to evaporate (thus, choice A is incorrect) which both reduces aerosol particle size and minimizes the "old freon" effect on the inspiratory maneuver.

Plastic chambers can develop an electrostatic charge that can attract charged aerosol particles to reduce output. Washing with a detergent reduces this charge. The chamber has no effect on the charge on the aerosol itself, therefore, choice D is incorrect. Finally, the presence of a one-way valve allows aerosol to be inhaled with subsequent exhaled gas diverted away from the chamber. This eliminates the washout of chamber aerosol by exhaled gas and permits subsequent inhalations from the chamber to maximize the delivered dose (thus, choice E is wrong).



D. Arterial PCO2 is reduced.

Pregnancy produces a variety of anatomic and functional changes to the respiratory system. Hormonal changes affect the upper airway, causing hyperemia, edema, and increased friability. The anatomy of the thoracic cage is altered by the expanding uterus and by hormonally induced ligamentous laxity. Although the diaphragm is displaced upwards, this is usually offset by an increase in the anteroposterior and transverse diameters and widening of the subcostal angle.

In healthy pregnant individuals,there is usually a 20 to 30% fall in arterial PCO2 to 28 to 32 mm Hg (therefore, choice D is correct). An increase in respiratory drive due to elevated serum progesterone levels is partly responsible and causes a state of relative hyperventilation that exceeds that required by the increase in metabolic CO2 production that also occurs with pregnancy. Similarly, tidal volume increases beginning in the first trimester and reaches 30 to 35% above baseline at term(choice C). In health, measurements of airflow are not significantly affected by pregnancy, because the increased diameter of the thoracic cage results in an increase in inspiratory capacity and preservation of FEV1 and vital capacity (choice A). Other anatomical changes in pregnancy produce alterations in lung volume that are measurable at 16 to 24 weeks gestation. Elevation of the diaphram and the gravid uterus cause a reduction of expiratory reserve volume by 8 to 40% and a decrease in residual volume by 7 to 22%. This is turn leads to a progressive decease in functional residual capacity (FRC) that reaches 10 to 25% by term (choice B). Despite these anatomical changes, alveolar-to-arterial oxygen tension gradient is similar to non-pregnant values, and mean arterial PO2 is usually greater than 100 mm Hg in healthy individuals (choice E).

Mild hypoxemia may develop in the supine position as FRC decreases near term, but more importantly, oxygen consumption also increases, reaching 20 to 30% above baseline at term. This combination can make the pregnant patient susceptible to the rapid development of hypoxia in the event of hypoventilation or apnea.



C. Nicotine patch at 22 mg per day.

The best smoking abstinence rates at 1 year have been achieved with the combination of bupropion plus nicotine patch. In a recent study, bupropion nearly doubled 12-month point-prevalence abstinence rates (30.3%) relative to placebo (15.6) or the patch (16.4%). The combination of bupropion and the patch was also more efficacious (35.5%) than placebo or the patch. Baced on the quantity of cigarettes smoked by the patient described in this case, the 22 mg/day patch is most appropriate.

Nicotine patches are available in doses of 7, 11, 14, 15, 21, and 22 mg. The “standard” over-the-counter nicotine patch is 21 or 22 mg. This dosage has been found to be sufficient to meet the nicotine needs of moderate smokers (approximately one pack per day). Heavier smokers may need higher doses to achieve initial abstinence and to prevent relapse. Nicotine patches are applied once daily not twice daily. The low dose Nicotine patch (7 mg) may not provide sufficient nicotine to meet this patient's initial needs. Nicotine gum is effective and comes in 2 mg and 4 mg dosages. In general, the 4 mg dose should be used by smokers who smoke greater than 20 cigarettess per day, which does not apply to the patient described in this case, who is smoking one half to one pack of cigarettes per day.

Bupropion is the only nonnicotine medication approved by the FDA for use in smoking cessation. This medication is marketed as Zyban for the stop-smoking indication and Wellbutrin for the antidepressant indication. It is important to ensure that the patient does not take both formulations.

The step-up does (the dose above which most patients do not derive additional benefit) for the antidepressant indication is 200 mg twice daily. Thus the combination of both formulations at the usual dosage would provide no additional benefit but would increase the possibility of adverse side effects. The initial dose for the smoking cessation indication is 150 mg/d of sustained release bupropion for 3 days, then a dose of 150 mg twice daily initiated 1 week before the patient's stop date. The usual length of treatment is 6 to 12 weeks but bupropion can be used safely much longer. The most common adverse effects are insomnia and dry mouth. As with other antidepressants, there is a small risk of seizures.

Typical long-term quit rates are as follows: no therapy =5%, brief advice only = 10%, and behavior therapy only = 15%. If medication (nicotine replacement or bupropion) is added, typical quit rates become: medication only = 10%, brief advice and medication = 20%, and behavior therapy and medication = 30%.



D. Temporal artery biopsy.

Temporal artery biopsy in this patient revealed giant cell arteritis. Polymyalgia rheumatica and giant cell arteritis most likely represent a spectrum of the same illness. The frequency of this illness increases after 50 years of age and peaks between 70 to 80 years of age. While there are no specific diagnostic tests, a number of validated criteria have been published. One such set of criteria was published in 1982. These criteria include: (1) age over 50 years; (2) bilateral aching stiffness or weakness involving more than one proximal muscle group; (3) erythrocyte sedimentation rate greater than 40 mm/h; and (4) exclusion of all other confounding diagnoses.

Our patient met all the criteria and the sore throat and tongue pain suggested that the temporal artery may be involved. Once the diagnosis of giant cell arteritis is established, glucocorticoid treatment should begin promptly at a dose of 60 mg/d to prevent visual loss. Cough and sore throat may be seen in up to 10% of the patients with giant cell arteritis and polymyalgia rheumatica and occasionally is seen as the presenting complaint. This is an unusual cause of cough, and the diagnosis should be considered after a careful history and elimination of other causes, using available guidelines.

Transthoracic echocardiogram (choice A) is not likely to help, because the patient has no cardiac symptoms or findings on physical examination. Induced sputum for culture after three courses of antibiotics is not likely to yield useful information, and in the presence of a normal chest radiograph tuberculosis and fungal infections are also not likely (choice B). Serum total and hemolytic complement levels (choice E) are not reduced in polymyalgia rheumatica and giant cell arteritis. Some individuals may consider a therapeutic trial of glucocorticoids (choice C). This practice should be discouraged, because once the drug is discontinued, rapid worsening of symptoms occur and occasional visual loss may follow.


C. Respiratory alkalosis and anion gap metabolic acidosis.

To solve this acid-base problem, the first step is to assess the internal consistency of the data using the Henderson-Hasselbalch or Henderson equation. The latter states [H+] = 24×PaCO2 / [HCO3-]. At pH 7.44, [H+] is 36 nmol/L. 36 = 24×24/16, so the data are consistent. Because the pH is > 7.40 and the PaCO2 is reduced, there is respiratory alkalosis.In this case, the normal pH with markedly reduced PaCO2 and serum bicarbonate points to a mixed acid-base disorder.

The next step is to determine whether there is a metabolic component to the acid-base disorder. The presence of an anion gap metabolic acidosis is detected by the presence of an increased anion gap, or [Na+]-([Cl-] + [HCO3-]). In this case, the anion gap is 135-(99 + 16), or 20. The normal anion gap is 12±4 mEq/L, so this patient has an anion gap acidosis, probably lactic acidosis due to sepsis and hypotension. Because acids are buffered by bicarbonate, each mEq/L increase in the anion gap leads to 1 mEq/L decline in the serum bicarbonate. If this is not the case in an acid-base problem, then there is a mixed disorder. Departures from the principle that an increased anion gap would correspond to a reduction in serum bicarbonate is expressed as the 揹elta gap, or (anion gap-12)-(24-bicarbonate). In pure anion gap metabolic acidosis, the delta gap should be zero, but measurement errors result in a normal delta gap in practice of 0±6. If the delta gap is positive, a simultaneous metabolic alkalosis or respiratory acidosis exists, whereas if it is a negative number, there is a concomitant hyperchloremic (nonanion gap) acidosis or chronic respiratory alkalosis. In this problem, the delta gap is (20-12)-(24-16), or 0, indicating the absence of these complicating conditions.




E. Add effective antimicrobial therapy for Staphylococcus aureus.

The primary concern in this patient is whether a secondary infection is complicating the primary influenza pneumonia. Diagnostic tests, such as bronchoscopy with bronchoalveolar lavage, will enable lower respiratory secretions to be obtained for quantitative cultures. However, these culture results are limited by both false negative and false positive results and, more importantly, a delay before the culture results are available. Consequently, bronchoalveolar lavage results are usually not helpful in determining initial antimicrobial therapy but may be helpful in adjusting antimicrobial therapy when culture results become available. Because of the clinical deterioration in this case, antimicrobial therapy should be inititated promptly and empirically. The choice of initial empiric antimicrobial therapy should be based on the organisms expected from the clinical circumstances. Numerous studies have shown that Staphylococcus aureus is often isolated as a secondary infections complication from either respiratory secretions or blood cultures in patients with influenza pneumonia. Consequently, providing appropriate antimicrobial therapy for S aureus would be the essential next step in this patient. Epidemiologic data have associated Pseudomonas aeruginosa with nososcomial pneumonia, especially ventilator-associated pneumonia, but this patient had not been intubated. Although antimicrobial therapy for P aeruginosa should have been an important consideration, the clinical circumstances pointed towards S aureus as the most likely secondary infectious agent.

Influenza pneumonia has a high mortality rate. In a recent series, 5 of 17 patients (29%) hospitalized with influenza pneumonia died, a rate similar to that described in the 1919 influenza pandemic. Death in influenza pneumonia is most often due to diffuse lung injury, with bilateral infiltrates seen on chest radiograph. Although neuraminidase inhibitors, such as oseltamivir, are effective in reducing symptom duration in uncomplicated upper respiratory tract infection with influenza, the limited information presently available suggests that oseltamivir does not reduce the mortality rate in influenza pneumonia. Similarly, limited information indicates that combination therapy with a neuraminidase inhibitor and amantadine does not reduce mortality rates in influenza pneumonia. A small study has suggested that corticosteroids might reduce mortality in patients with unresolved ARDS, but corticosteroids should only be used after underlying pulmonary infections had been excluded. In this case, corticosteroids would not have been appropriate because of the concern about secondary bacterial infection.


A. Higher colonization rate of Pseudomonas aeruginosa. Staphylococcus aureus is the usual organism that first colonizes young people with cystic fibrosis. Later, as the disease progresses, this organism is replaced by Haemophilus influenzae or Pseudomonas aeruginosa. It has long been thought that eradication of S aureus might lead to long-term benefits. In a recently published trial, young children with cystic fibrosis in previously good health were randomized to receive oral cephalosporin therapy or placebo. Cephalosporin therapy was associated with a subsequent higher rate of coloization with P aeruginosa (choice A). This colonization was also associated with increased pulmonary symptoms. Treatment with antibiotics had no impact on hospitalizations (choice B), lung-function measurements (choice C), or respiratory symptoms (choice D). colonization rates of S aureus were reduced with oral cephalosporin therapy (choice E). From these data, it appears that prophylactic antibiotics not only fail to benefit cystic fibrosis patients but also appear to encourage colonization with P aeruginosa with a subsequent increase in respirtory symptoms.


D. Blood culture.

Although infection with the Gram-positive Bacillus anthracis rarely cause disease in humans (ie, anthrax), several nations and terrorist groups are believed to have offensive biological weapons programs, and some are working with anthrax. Infection is caused by endospores that are introduced through skin abrasions, ingestion, or inhalation. In 2001, there were six cases and three fatalities from inhalation anthrax in the United States, attributed to intentional exposure of victims through the mail. Six more cases of cutaneous anthrax were documented, and many more persons with potential exposure showed antibody responses to the anthrax bacillus, with no mortalities.

When dispersed as an aerosol, anthrax spores can be a hazard many miles from the point of release, rendering it a formidable biologic weapon. After inhalation, anthrax spores are deposited in the alveoli, engulfed by alveolar macrophages, and transported to peribronchial and mediastinal lymph nodes. Even though the lungs are the routes of entry, pneumonia is unusual. Rather, germinating spores multiply and secrete pathogenic exotoxins that cause hemorrhagic lymphadenitis and mediastinitis, followed by high-grade bacteremia and exotoxemia causing shock and death. Hemorrhagic meningitis is also seen in approximately half of cases with severe illness.

The diagnosis of inhalational anthrax requires a high index of suspicion because the initial symptoms are nonspecific. Blood cultures are usually positive within 24 hours, but the laboratory should be alerted to the possibility of anthrax so the appropriate biochemical tests are performed. In fact, the bacterial burden is so high that Gram's stain of unspun blood may show Gram-positive bacilli. The finding of a widened mediastinum in a previously healthy patient with an overwhelming flulike illness strongly suggests this infection, but treatment at this stage of illness is unlikely to lead to survival. Chest CT scanning in this patient would probably show hemorrhagic mediastinitis or lymphadenitis, but would not be diagnostic. Ciprofloxacin is recommended as the initial therapy of anthrax because of resistance of natural strains to other classes of antibiotics, but penicillin or doxycycline are considered optimal therapy if the strain is shown to be susceptible.

Gram's stain of sputum would not be expected to show organisms, as pneumonia is uncommon in anthrax. Mediastinal widening and pleural effusions suggest the possibility of extrapulmonary tuberculosis, especially in persons with HIV infection. Sputum smears and cultures are sometimes positive in patients with extrapulmonary tuberculosis and normal lungs on radiograph, and pleural biopsy histology and cultures are usually diagnostic with tuberculous effusions, but this patient has no apparent risk factors for tuberculosis. Viral cultures would not be helpful because no viral pathogen causes this constellation of findings.




A. Quantitative serum immunoglobulins.

Women with non-Hodgkin's lymphoma have a markedly increased incidence of acquired hypogammaglobulinemia that often present as chronic, recurrent sinusitis and bronchiectasis. Quantitative immunoglobulins were obtained and revealed markedly decreased levels of IgG, IgA, and IgM. She was begun on gamma globulin replacement therapy and then re-treated with moxifloxacin. Her cough improved markedly, and over the next year she had only occasional exacerbations that usually occurred just prior to her next immunoglobulin dose and then promptly improved with treatment.

A sweat chloride test (choice B) is a reasonable consideration, but because of her age and the non-Hodgkin's lymphoma, testing for hypogammaglobulinemia should be done first. Choice C is incorrect because one should measure total immunoglobulin class levels before considering a subclass deficiency. IgG subclass deficiencies have been associated with bronchiectasis, but this test is not routinely available and large-scale normal population reference values are not available. Choice D is incorrect because the lack of a history of asthma, no evidence of central bronchiectasis, and a normal total IgE and eosinophil count make allergic bronchopulmonary aspergillosis extraordinarily unlikely. Answer E is incorrect because bronchiectasis (and infection with Streptococcus pneumoniae) is much less likely to be due to a T-cell related abnormality than B-cell related immunoglobulin deficiency.

Bronchiectasis is an abnormal and permanent dilatation of bronchi (commonly at the subsegmental level). It can either present as focal localized disease of a segment or lobe or as a generalized process present in multiple parts of both lungs. Localized disease often is a sequela of focal airway obstruction or previous infection. More diffuse bronchiectasis is often associated with a humoral immunologic abnormality such as hypogammaglobulinemia (or selective immunoglobulin deficiencies involving an IgG subclass, isolated IgE, IgM, or IgA). Associated chronic sinusitis is often present. Other causes of generalized bronchiectasis (usually with associated sinus disease) include cystic fibrosis, dyskinetic cilia syndromes, and Young's syndrome (obstructive azoospermia and generally mild chronic sinopulmonary infections). Systemic diseases associated with bronchiectasis include rheumatoid arthritis (or other collagen vascular diseases) and inflammatory bowel disease. An immunologic or structural abnormality (eg, humoral abnormality, primary cilia dyskinesia, cystic fibrosis) is more commonly found in children or young adults, whereas in older adults a history of prior pneumonia is more common. Primary Mycobacterium avium complex infection (particularly in a middle-aged Caucasian woman with unexplained chronic cough) and allergic bronchopulmonary aspergillosis are also important considerations. Other rare cuases of bronchiectasis include alpha-1-antitrypsin deficiency and Mounier-Kuhn disease (tracheobronchomegaly).



B. Was effective for improving functional status (but not survival) overall and provided a survival benefit in a prospectively identified subgroup with upper lobe predominance and poor functional status.

The best answer is B. Lung volume reduction surgery (LVRS) is a surgical technique that removes over-inflated regions of lungs in emphysema patients. The procedure can be done through either a median sternotomy or through a thoracoscopic technique. LVRS is thought to improve lung function in severe emphysema by two mechanisms: (1) By removing grossly overdistended lung regions, healthier but previously compressed regions will be allowed to normally expand; and (2) the lung volume reduction will allow the previously flattened diaphragm to return to a more normal configuration.

There has been much controversy about who would be the best candidates for this type of surgery. In small series, hypercarbia, homogeneous disease, and reduced DLCO seemed to predict poorer outcomes. The recently completed National Emphysema Treatment Trial (NETT) enrolled over 1,200 patients with emphysema and randomized them to either medical therapy or LVRS. Up to 5 years of follow-up for mortality, functional status, and quality of life was planned. An early interim analysis revealed a subgroup with a particularly poor surgical outcome (16% 30-day mortality). This subgroup is characterized by FEV1 < 20% predicted and either a DLCO < 20% or homogeneous disease on chest CT (making choice C incorrect).

Final analysis of 29 month follow-up in the entire cohort has recently been published and showed significantly better functional status and health-related quality of life in the patients randomized to LVRS (thus, choice E is incorrect). Overall survival was comparable between the two groups, even accounting for early surgical mortality (therefore, choice A is incorrect). Prospectively planned subgroup analysis showed and additional survival benefit to LVRS in patients with upper lobe predominance and poor functional status pre-surgery (thus, choice B is the correct answer). Pre-operative PaO2 was not a significant predictor of outcome (choice D).


C. Recent arrivals from a high prevalence country.

Recent arrivals from a high prevalence country are considered to be positive if their tuberculin skin tests are ≥10 mm of induration (choice C). The prevalence of TB determines the likelihood that a positive tuberculin skin test reflects latent tuberculous infection. Based on the sensitivity, specificity, and prevalence of TB in different groups, three separate cut points have been recommended for defining a positive test response. Among individuals who are at the greatest risk of developing TB, a cut point of 5 mm has been recommended. Among these people, the prevalence of tuberculosis is 25 to 50%, and with a specificity of 0.99 of the tuberculin skin test in this population, the positive predictive value of the test approximates 99%. These include individuals with abnormal chest radiographs consistent with TB (choice D) or persons who have been in close contact with an active case of TB (choice B). Others that would be included for consideration would be immunosuppressed patients (including those who are HIV-positive) (choice A) and organ transplant recipients, particularly those who are receiving corticosteroids (choice E).



D. Local infusion of thrombolytic therapy into the pulmonary artery.

In this unusual case of a patient with massive pulmonary emboli and hemodynamic instability, time is a critical factor in any intervention. The usual treatment approach of systemic thrombolytics, which is preferred over heparin when acute massive pulmonary emboli cause shock, is contraindicated because the patient's hematuria represents bleeding from a noncompressible vessel. There is little published information other than abstracts on the value of local infusion of thrombolytics as a treatment modality for pulmonary emboli. These reports suggest that local infusion of thrombolytics into the pulmonary artery might result in rapid clot lysis with little systemic anticoagulant effect. In this patient, local infusion of a thrombolytic into the pulmonary artery resulted in prompt improvement of both hemodynamics and oxygenation without worsening the hematuria.

Surgical removal of massive pulmonary emboli complicating renal cell carcinoma has been described. However, these are complicated procedures involving removal of the primary tumor through an abdominal approach in addition to pulmonary embolectomy under cardiopulmonary bypass. Including an abdominal approach to remove the primary tumor is important because a combination of venous thrombosis and tumor extension into the renal vein and the inferior vena cava will most probably have been the source of the pulmonary emboli. If the primary tumor and associated clot were left in place following a pulmonary embolectomy, the patient would remain at very high risk for subsequent pulmonary emboli. An inferior vena cava filter, which is typically placed below the renal veins, would not adequately protect the patient. Trying to place a vena cava filter above the renal veins would be technically demanding if tumor and clot extended from the renal vein into the inferior vena cava. In some cases, tumor and clot have extended into the right atrium. A trial of local infusion of thrombolytics is a reasonable approach prior to resorting to extensive surgical procedures. A variety of suction and thrombectomy devices are being developed to remove clot percutaneously, but these devices pose the risk of disruption of the clot with distal embolization.

Renal cell carcinomas are generally resistant to chemotherapeutic regimens. There may be a 15 to 20% response rate to therapy with interleukin-2 and/or interferon-a, but this response is usually not immediate.


B. Buffering of hypercapnic acidosis with bicarbonate worsens acute lung injury.

Lung protective mechanical ventilation strategies often result in "so-called" permissive hypercapnia. Because physicians associate academia with hypoperfusion and end-orgean failure and because there is concern for adverse hemodynamic effects of acidosis, some authorities recommend the use of bicarbonate therapy to keep blood pH above 7.20. However, there is little to no evidence that this is beneficial. To the contrary, there is strong experimental evidence that buffering hypercapnic acidosis worsen acute lung injury in ex vivo perfused mechanically ventilated lungs and that hypercapnia per se may exert clinically important organ protection. One proposed mechanism by which hypercapnic acidosis may protect the lungs from injury is inhibition of endogenous xanthine oxidase enzyme activity and the consequent reduction in free radical generation. This mechanism has been examined in detail in lung models of ischemia/reperfusion injury. Alternative mechanisms involve pH-dependent alterations in amiloride sensitive Na-H exchange channels. These microvascular ion channels are important in regulating pulmonary fluid flux. Consistent with this hypothesis is the observation that the administration of bicarbonate raises the pulmonary capillary filtration coefficient and promotes edema formation in isolated perfused lungs.

Not only is there evidence that hypercapnic acidosis may be organ protective, there is also evidence that hypocapnic alkalosis has adverse effects on neurologic and cardiovascular outcomes. Hypocapnia accentuates ischemic injury to the brain and myocardium and worsens systemic oxygenation. There is strong evidence that systemic pH regulates the rate of endogenous acid production and that buffering with bicarbonate interferes with this homeostatic mechanisms. For example, the administration of bicarbonate increases the rate of lactate production and raises blood lactate concentration. Option A is therefore incorrect. The same holds true for ketone generation in diabetic ketoacidosis; bicarbonate increases ketone formation as opposed to reducing it as stated in option C. while there are no data to refute the common practice of alkali therapy in severe cases of "permissive hypercapnia," there are equally no data to suggest clinical benefit. Therefore, answer D is incorrect. Finally, the homeostatic feedback mechanism between pH and acid production has implications for metabolic rate; academia lowers oxygen demand, alkalemia increases it. Option E is therefore incorrect.


E. The risk of a fatal asthma episode is greatest for asthmatics with severe disease and fixed airflow obstruction.

The greatest risk of a fatal outcome in asthma appears to be in those patients who demonstrate the highest degrees of airway hyperresponsiveness and FEV1 lability, rather than in those with severe but fixed airflow obstruction. In one study, the relative risk of death from asthma was seven times higher for patients who demonstrated a 50% or greater increase in FEV1 in response to bronchodilator, compared to those whose FEV1 improved by less than 25%. While this observation might seem somewhat contrary to expectations, it emphasizes that the most important result of poor asthma control is the persistence of excessive airway lability, with its attendant risk of asthma exacerbation. Persisting FEV1 lability is most common among smokers and those with persistent atopic asthma. Other documented risk factors for asthma mortality include age > 40 years, smoking, and blood eosinophilia. Middle-aged and older adults with asthma rarely achieve complete remission. The remission rate in adults is also substantially lower than in children (10% to 15% vs over 50%). In a 25-year study of adult asthma, remission, which was defined as becoming asymptomatic with normal FEV1 and normal airway responsiveness, was noted in only 20 of 190 subjects (10.5%). In this study, remission was associated with milder asthma and younger age at first diagnosis, together with male gender and less initial airway hyperresponsiveness. Control of asthma symptoms, FEV1, and airway hyperresponsiveness also appears to be influenced by the timing of the introduction of inhaled corticosteroids (ICS). Several trials have shown that FEV1 is much less likely to normalize if the institution of ICS is delayed following the initial diagnosis of asthma. Similar to the situation in COPD, several longitudinal studies have demonstrated a more rapid age-related decline in FEV1 in adult asthmatics compared to the nonasthmatic population, and this is further compounded by smoking. There are few long-term studies of the effects of treatment on the natural history of asthma. However, a recent study of asthmatics aged 5 to 44 years has clearly demonstrated a dose-dependent reduction in asthma mortality with increasing use of ICS, in that the death rate from asthma was reduced by approximately 50% with the use of 6 or more canisters of ICS during a 12-month period, compared to patients who used smaller amounts of ICS.


D. Repeated bouts of exercise worsen the degree of EIB.

Exercise does not cause asthma, but rather is considered an indirect stimulus to bronchoconstriction in people with asthma (choice E). Therefore the term "exercise-induced bronchoconstriction"(EIB) is preferred over the obsolete term "exercise-induced asthma."EIB occurs in 70 to 80% of patients with actively symptomatic asthma, and is more likely to occur in patients with moderate to severely increased airway responsiveness. Thus, the frequency and magnitude of EIB can be regarded as an index of the adequacy of asthma control. EIB is most likely caused by the efforts of the airways to condition to body temperature and to fully humidify the increased volumes of air inhaled during exercise; it appears to be mediated primarily by the release of cysteinyl leukotrienes. This may explain why the magnitude of EIB has been shown to be diminished by nasal breathing during exercise compared to mouth breathing (choice C), and by the use of leukotreine receptor antagonists, often in combination with bronchodilators and inhaled corticosteroids.

Although EIB occasionally occurs during exercise itself, exercise is much more commonly accompanied by bronchodilation that lasts for 1 to 3 minutes after exercise (choice B). With EIB, bronchoconstriction typically begins shortly after exertion, peaks within 10 to 15 minutes, and resolves by 60 minutes (choice A). In many patients with EIB, the episode of bronchoconstriction is followed by a period during which repeat exercise causes less bronchoconstriction, and in some cases, with repeated bouts of exercise, the bronchoconstriction can be abolished (choice D). This period of exercise refractoriness lasts less than 4 hours, but is often used by elite athletes with EIB to both enhance training and prevent major EIB during competition.



A. Reduce pulmonary vascular pressure elevations associated with nocturnal oxyhemoglobin desaturation.

The correct choice is A. Nocturnal oxygen desaturation (NOD), depending upon how it is defined (Sao2 < 90% for 30% of sleep; Sao2 < 90% for > 5 minutes of sleep; Sao2 < 85% during REM sleep), occurs in 25 to 45% of COPD patients. The mechanisms for NOD in this population include nocturnal hypoventilation (worse in REM sleep) and ventilation/perfusion mismatch due to poor diaphragmatic function in the supine position.

Elevations in pulmonary artery pressure are common in COPD patients with NOD. Because of this, daytime symptoms may mimic other sleep disorders that produce pulmonary hypertension (eg, peripheral edema and reduced exercise capacity). Diagnostic considerations should thus include other specific sleep disorders although NOD often exists without them in the COPD population.

Supplemental oxygen in COPD patients with adequate awake values for Sao2 but who exhibit NOD has been shown to lower pulmonary artery pressures (choice A). This is important because retrospective analyses have suggested an increased mortality for COPD patients with NOD as compared to those without NOD, and one of these studies suggested that supplemental oxygen may reduce this mortality. However, no prospective randomized studies exist that address either this mortality issue or issues of functional status or pulmonary function tests (therefore, choices B, C, D, and E are wrong).

Medicare regulation allows for payment for supplemental oxygen during NOD using the standard criteria of Pao2≤55 mm Hg or Sao2≤88% (55 to 60 mm Hg or Sao2 88 to 90% if cor pulmonale, right heart failure, or erythrocytosis are also present) without stipulating the duration of the hypoxemia. Supplemental O2 for NOD can also be reimbursed if there is a documented drop in Pao2>10 mm Hg or Sao2>5% along with symptoms of nocturnal hypoxemia defined by Medicare as impaired cognitive function, restlessness or insomnia.


B. The chest radiograph is normal or unchanged.

Although it can sometimes be clinically silent, the signs and symptoms of acute lung rejection include cough, dyspnea, and low-grade fever. During the first 3 months after transplantation the chest radiograph is often, but not always, abnormal during acute rejection. The typical finding is a perihilar interstitial infiltrate, but other abnormalities have been described. However, the radiographic pattern is not specific for acute rejection, and confirmation by transbronchial lung biopsy is important to distinguish rejection from cytomegalovirus pneumonia or other problems with a similar presentation. After the third posttransplant month, the chest radiograph is usually normal or unchanged during episodes of acute rejection. Nevertheless, the chest radiograph is useful to exclude other problems.

After heart-lung and lung transplantation, acute rejection is usually diagnosed by transbronchial lung biopsy. Transbronchial biopsy is a sensitive and safe procedure in heart-lung and lung transplant recipients, and a surgical lung biopsy is rarely needed to diagnose acute rejection. The pathognomonic histologic feature of acute rejection is a perivascular lymphocytic infiltrate. Sometimes this is accompanied by a lymphocytic bronchiolitis or bronchitis. However, bronchiolitis obliterans is the pathologic hallmark of chronic allograft rejection, not acute rejection. Bronchoalveolar lavage (BAL) fluid analysis has been a useful tool in understanding rejection, but the BAL cell profile does not reliably distinguish acute rejection from infection or other problems. As in other areas, its clinical utility in heart-lung and lung transplantation is to aid in the diagnosis of pulmonary infection.

Heart and lung rejection are usually discordant in heart-lung transplant recipients; concordant cardiac rejection occurs in less than one third of episodes of lung rejection. Thus, cardiac rejection cannot be used to diagnose or monitor lung rejection after heart-lung transplantation. However, the features of lung rejection are similar in heart-lung and isolated lung transplant recipients.


D. Insulin resistance is more common in OSA patients, even after adjustment for body mass index (BMI).

Obstructive sleep apnea (OSA) is a highly prevalent condition in the United States. Although estimates vary based on the study and population, it has been suggested that a minimum of 5% of adults have OSA, a prevalence similar to asthma. Population-based studies have shown that a number of cardiovascular diseases are associated with OSA and recent data have also conclusively shown that glucose intolerance and insulin resistance are increased in OSA independent of age and obesity (choice D). The pathophysiology appears to be related to sleep-related hypoxemia and sleep deprivation.

There are a number of risk factors proposed to play an important role in the development and, perhaps, progression of OSA. It is very clear that OSA is more common in adult men than in adult women. Prevalence estimates suggest this risk is on the order of 2- to 3-fold (not 6- to 8-fold as suggested in choice A). The reason for this is not clear, although possible hypotheses include hormonal differences, differential fat deposition, craniofacial morphology, and genioglossus muscle activation. OSA prevalence does appear to increase following menopause. The effect of aging, independent of menopause, has also been investigated in epidemiologic studies. Interestingly, OSA is extremely prevalent in elderly populations, ranging from 2 to 4 times higher than what is seen in middle age. Some studies have shown the prevalence (using and AHI≥5 per hour) as high as 80% in patients older than 71 years of age (therefore choice B is incorrect).

As mentioned above, cardiovascular disease is linked to OSA. Coronary artery disease and stroke have been associated with OSA. A number of studies have shown that hypertension is very common in OSA; 30% of patients in essential hypertension clinics have OSA. The Sleep Heart Health Study, a longitudinal study of adults ages 40 to 98, published a cross-sectional analysis of their initial polysomnography studies which showed that the odds ratios for the presence of hypertension increased with increasing AHI levels. The Wisconsin Sleep Cohort Study, another longitudinal study of adults ages 30 to 60, showed that for even small elevations in AHI (1 to 5) at baseline, there was an increased likelihood of developing hypertension at the 4- and 8-year follow-up studies (therefore choice C is incorrect). These are suggestive of a clear relationship between OSA and hypertension but cannot prove causality. If evidence were to show that treatment of OSA decreases blood pressure in hypertensives, it would also strengthen the association. Although numerous studies have tried to confirm that OSA treatment reduces blood pressure, the results are inconsistent and firm conclusions cannot be made at this time (therefore choice E is incorrect).



A. Humidification.

Nebulizers and metered-dose inhalers (MDIs) are used to deliver aerosolized medications into the airways of ventilated patients. Most studies of these devices have been performed with the bronchodilator class of medications. A variety of factors affect the delivery of aerosolized drugs. The droplet size is the most important characteristic and is usually defined by its mass median aerodynamic diameter (MMAD). With MDIs, the MMAD may initially exceed 30 to 40 mm, but as the particles travel through the circuit and airway, the propellants evaporate and particles decrease in size to the range of 2 to 5 mm. It has been shown that particles must be 0.5 to 2 mm to penetrate to the alveoli.

Humidification of the ventilator circuit has been consistently shown to decrease aerosol delivery with both MDIs and nebulizers. This is because therapeutic aerosols are hygroscopeic and grow larger in the presence of humidity. This subsequently results in large airway (proximal) deposition. It has also been shown that the position of the MDI at the end of the endotracheal tube, rather than in the inspiratory circuit, decreases aerosol deposition. Use of an inspiratory pause will improve aerosol delivery, as will the use of a spacer device. The spacer device should be placed in line in the inspiratory limb for the highest drug delivery. Use of a decelerating or sinusoidal waveform has been shown in a ventilator model to deliver more drug than use of a square waveform. It has also been shown that more drug is delivered during volume (or pressure-support) ventilation than during spontaneous ventilation.


C. Packed red cell transfusion

This patient is presenting with the acute chest syndrome (ACS) of sickle cell disease (SCD). ACS is the leading cause of death in patients with SCD. The acute chest syndrome affects about 40% of all people with sickle cell anemia. It is most common in children and, when recurrent, can lead to chronic respiratory insufficiency. In a large multicenter study, 13% of patients with ACS developed respiratory failure requiring mechanical ventilation, and 3% died, largely due to infection and embolism (bone marrow, fat, or thrombotic). This syndrome is defined clinically with findings of chest pain, fever, and new infiltrates on chest radiograph. Pathologic causes include infection, in situ thrombosis, fat embolism (from bone infarctions), and hypoventilation secondary to pain and narcotics administered for treatment. Infection and/or fat embolism can precipitate sickling of cells, hypoxemia, and ischemia resulting in pain often in the chest and extremities. Management includes transfusions, particularly in those patients with serious cases of ACS (ie, hypoxemia and/or respiratory distress), those with a history of cardiac disease, those with significant pain in the extremities, and in adults. Other indications for transfusion include significant anemia, thrombocytopenia, and/or the presence of multilobar pneumonia. Studies have shown improved oxygenation following simple or exchange transfusion.

Patients with SCD are also predisposed to pneumonias, particularly pneumococcal pneumonia, and are also more prone to infections with drug-resistant strains because of immunosuppression due to autosplenectomy. Infections with atypical organisms (including chlamydia or mycoplasma) are also well described and treatment recommendations include broad-spectrum antibiotics including a macrolide. Pseudomanal infections are not common infections in patients with SCD and changing antibiotic coverage would not be the next best step in this patient's management. It is unclear if patients with ACS are at increased risk of thromboembolic disease, and heparin is not standard in the initial management, particularly if there are radiographic infiltrates present. Corticosteroids have been shown to be beneficial in anecdotal cases of refractory ACS, but are not standard in initial therapy. Long-term treatment with hydroxyurea results in increased production of fetal hemoglobin and decreased polymerization. There is a 50% reduction in painful crises and episodes of acute chest syndrome. However, there is no role for this medication in the acute management of patients with this syndrome. All patients should be given supplemental oxygen. Narcotic analgesia is also standardly used in the treatment of ACS. Bronchodilators are recommended even in the absence of obvious bronchospasm because airway hyperreactivity is frequently present. Incentive spirometry has been shown to reduce pulmonary complications in SCD.


E. Order a ventilation-perfusion scan

The most likely diagnosis in this patient with nephrotic syndrome with a unilateral bloody pleural effusion is pulmonary embolism. His ventilation-perfusion scan showed multiple unmatched segmental perfusion defects. Other causes of a pleural RBC count of greater than 100,000/mm3 (100*109L) include trauma, malignancy, postcardiac injury syndrome, and asbestos pleural effusion. None of these conditions are clinically relevant in our patient. Pulmonary embolism is the fourth leading cause of pleural effusions (150,000 per year) in the United States. Pleural effusions occur in up to 50% of patients with pulmonary embolism, with 20% being transudates. The pleural fluid appears bloody in up to two thirds of patients. Leukocyte counts vary widely and show an early neutrophil predominance followed by a lymphocytic predominance. Glucose values approximate serum values. A bloody effusion is not a contraindication to full dose anticoagulation.

Patients with nephrotic syndrome have a hypercoagulable state for multiple reasons, including (1) loss of clotting inhibitors (antithrombin III and protein S) in the urine; (2) abnormal platelet aggregation; and (3) hypoalbuminemia stimulates hepatic production of coagulation factors (V, VII, X, and XII), fibrinogen, and fibronectin. Up to 30% of nephrotic syndrome patients develop pulmonary embolism, which may be "linically silent" as in our patients. Anticoagulation with heparin may be difficult in nephrotic syndrome patients because of low antithrombin III levels. Transudative pleural effusions also develop in patients with nephrotic syndrome, but unilateral or asymmetrical bilateral pleural effusions should alert the clinician to the possibility of a pulmonary embolism.

A contrast CT scan of the chest (choice A) is relatively contraindicated in this patient with significant renal insufficiency. Corticosteroids (choice B) are utilized for therapy of membranous nephropathy, the most common cause of nephrotic syndrome. However, the underlying cause of this patient's nephrotic syndrome is not known currently. A therapeutic thoracentesis (choice C) may improve the patient's dyspnea; however, it would not address the underlying etiology of his pleural effusion. Placing a thoracotomy tube (choice D) would be indicated for a hemorrhagic pleural effusion in the setting of trauma or hemothorax, but not in this clinical setting.


A. Maximal voluntary ventilation.

The pattern of pulmonary function abnormalities (a decreased FVC, an increased FEV1/FVC ratio, an increased residual volume, and a relatively well maintained total lung capacity) suggests a neuromuscular disease. A reduced maximal voluntary ventilation (MVV) would support this diagnosis and would also be a useful baseline index for following disease progression. An advantage to MVV is that it can be performed with a spirometer. The test consists of having the patient breathe as fast and as deep as possible over a 12 to 15 second time interval. Other tests useful for both confirming neuromuscular disease and following disease progression would be maximal nasal sniff pressure tests, PImax and PEmax. The history, reported chest radiograph interpretation, and pulmonary function abnormalities do not suggest either obstructive airway disease or an interstitial processs.

Of the various neuromuscular diseases to be considered, the clinical presentation in this case is most consistent with the diagnosis of amyotrophic lateral sclerosis. This disease usually affects patients older than 50. The presenting symptoms of amyotrophic lateral scleraosis are typically related to weakness and clumsiness of the hands. As weakness progresses, atrophy and fasciculations of the affected muscles become apparent. Involvement of the muscles of the lower extremeities, trunk, and neck, as well as diaphragmatic weakness, usually follow. However, up to 25% of patients with amyotrophic lateral sclerosis may present with a progressive bulbar palsy involving muscles of the jaw, face, tongue, pharynx, and larynx. Chewing and swallowing become difficult and aspiration of liquids may occur. Although cough is an atypical presenting symptom for amyotrophic lateral sclerosis, chronic cough has been associated with pharyngeal dysfunction. The association of cough with drinking and the drooling after eating should suggest progressive bulbar palsy. Myasthenia gravis, another possible consideration, is less likely because it typically presents in younger women.