5. • A 62-year-old woman who has idiopathic
pulmonary fibrosis (IPF) has rapidly worsening
dyspnea over the past 3 weeks.
• She was diagnosed with IPF by CT scan and
surgical lung biopsy 1 year ago.
• At that time, she started to receive prednisone
and cyclophosphamide and had been fairly
stable until these past few weeks
6. • On physical examination:
She is in mild respiratory distress.
Her BP is 118/68 mm Hg,
Temperature is 37.6C,
Heart rate is 115/min,
Respiratory rate is 22/min, and oxygen
saturation is 90% on 4 L/min supplemental
oxygen, increased from a baseline of 2 L/min.
7. • She has no jugular venous distention or neck
adenopathy.
• She is tachycardic without any extra heart
sounds or murmurs.
• Lung examination reveals bibasilar crackles
without any signs of focal consolidation.
• There was no peripheral edema.
8. • Her chest radiograph reveals diffuse patchy
opacities and bibasilar reticular markings.
• Her CBC is remarkable for a WBC count of
8,700/L (8.7 × 109/L), with 60% neutrophils,
1% bands, 20% lymphocytes, 18% monocytes
and 1% eosinophils.
• Brain natriuretic peptide level is 100 pg/mL
(100 ng/L)
9. • Serial troponin T levels are not
elevated.
• Blood, sputum, and urine culture
results are negative.
• CT pulmonary angiogram does not
reveal any evidence of pulmonary
embolism.
10. Which of the following statements about her
diagnosis is correct?
A. The CT angiogram will demonstrate progression
of interstitial disease and increased cyst
formation.
B. Bronchoalveolar lavage will reveal an eosinophilic
cellular infiltrate.
C. Lung biopsy will show changes consistent with
diffuse alveolar damage.
D. Most patients will have a favorable response to
pulse treatment with corticosteroids
11. • This patient meets the diagnostic criteria for
an acute exacerbation of IPF (AE-IPF):
Worsening of dyspnea within the past month,
Increased hypoxemia,
New pulmonary opacities on chest
radiography,
The absence of apparent infection or heart
disease.
• AE-IPF is an acute insult to the lung with a
background of IPF, and the pathologic changes
reflect this fact.
12. • The histopathologic findings reveal hyaline
membranes lining the alveoli, type II
pneumonocyte proliferation, and interstitial
inflammation and fibrosis, ie, diffuse alveolar
damage over and above the underlying usual
interstitial pneumonia (choice C is correct)
13. • IPF is often thought of as a slow, but inevitable
decline in pulmonary function.
• However, newer data suggest that, in many
patients, the disease is characterized by only
minimal physiologic deterioration but
frequent hospitalizations for respiratory
disorders and an acute and rapid progression
of lung disease in almost half the patients who
die from IPF.
• The incidence of this acute decline in all
patients with IPF appears to be around 10% to
15%/year
14. • As noted above, AE-IPF is defined as rapid
deterioration during the course of the disease
that is not due to infection, pulmonary embolism,
or heart disease.
• It is crucial to rule out these latter possibilities, as
treatment for one condition could be fatal for the
other.
• Rapidly progressive dyspnea is the most common
symptom, although patients may also complain
of a nonproductive cough and low-grade fevers.
No clear risk factors have been identified, and
there is often no identifiable trigger
15. • The pathogenesis is not clear. Evidence suggests
that IPF involves multiple microscopic injuries to
the lungs that are temporally distributed over
many years. These injuries lead to inflammation
stimulated by an imbalance in T-helper type II
cells and subsequent cytokine release and
fibroblast proliferation.
• These injuries likely account for the temporal
heterogeneity seen in UIP and may also be
responsible for more acute episodes
characterized by a rapid decline in lung function.
16. • Chest radiographs will reveal new opacities, and CT
scans will show new-onset diffuse ground-glass
opacities (GGO) and/or consolidation on the
background of the existing fi brosis and
honeycombing (HC) (choice A is incorrect).
• Bronchoscopy with BAL is often done to exclude
infection and will typically show BAL neutrophilia,
large numbers of alveolar macrophages, and
desquamated alveolar cells with varying degrees of
nuclear atypia (choice B is incorrect).
17.
18. • There are no large trials on treatment. Most
patients are given a pulse of
methylprednisolone and their usual steroid
dose is increased. If they are not already
receiving another immunosuppressive agent,
one may be added.
• Unfortunately, reported patient series show
that a large percentage of patients will go on
to require mechanical ventilatory support, and
the majority of these patients will die of
respiratory failure (choice D is incorrect).
19. SO which of the following statements about her
diagnosis is correct?
A. The CT angiogram will demonstrate progression
of interstitial disease and increased cyst
formation.
B. Bronchoalveolar lavage will reveal an eosinophilic
cellular infi ltrate.
C. Lung biopsy will show changes consistent with
diff use alveolar damage.
D. Most patients will have a favorable response to
pulse treatment with corticosteroids
20.
21. Acute exacerbations in patients
with idiopathic pulmonary fibrosis
By
Gamal Rabie Agmy , MD , FCCP
Professor of Chest Diseases ,Assiut University
22. Histopathological Patterns of IIPs
Thannickal VJ, et al. Annu Rev Med. 2004;55:395-417.
Age
Genetic factors
Environmental factors
Nature of injury
– Etiologic agent
– Recurrent vs single
– Endothelial vs epithelial
Histopathologic Pattern
DIP RB-ILD LIP COP NSIP AIP UIP
Inflammation
Fibrosis
LUNG INJURY
24. 50%
Years
Respiratory
Function/Symptoms
1 2 3
Acute exacerbation
Step Theory of UIP/IPF Progression
Progression of IPF: Acute Exacerbation vs
Slow Decline
FVC
0 4
Am J Respir Cell Mol Biol. 2003;29(3 suppl):S1-S105.
=hits
25. Multiple Hypotheses for the
Pathogenesis of IPF
• Inflammation causes fibrosis
• Noninflammatory (multiple hit) hypothesis:
fibrosis results from epithelial injury and
abnormal wound healing in the absence of
chronic inflammation
• Vascular remodeling: aberrant vascular
remodeling supports fibrosis, and may contribute
to increased shunt and hypoxemia
Noble PW, Homer RJ. Clin Chest Med. 2004;25:749-758, vii.
Raghu G, Chang J. Clin Chest Med. 2004;25: 621-636, v.
Strieter R. Am J Respir Cell Mol Biol. 2003;29(3 suppl):S67-S69.
26. • Inflammation causes fibrosis
– Inflammatory concept was dominant in the 1970s and
1980s
• IPF resulted from unremitting inflammatory response
to injury culminating in progressive fibrosis
– Role of inflammation remains controversial
• Lack of efficacy of corticosteroids
Noble PW, Homer RJ. Clin Chest Med. 2004;25:749-758, vii.
Raghu G, Chang J. Clin Chest Med. 2004;25:621-636, v.
Injury Inflammation Fibrosis
Inflammatory Hypothesis
29. • Fibrosis results from epithelial/endothelial injury
and abnormal wound healing in the absence of
chronic inflammation
– Recurrent, unknown injury to distal pulmonary parenchyma
causes repeated epithelial cell injury and apoptosis
– Loss of alveolar epithelium exposes basement membrane
to oxidative injury and degradation
– Failure of re-epithelialization/re-endothelialization provides
stimulus for persistent profibrotic growth factor production,
persistent fibroblast proliferation, excessive deposition of
ECM, and progressive fibrosis
Noble PW, Homer RJ. Clin Chest Med. 2004;25:749-758, vii.
Raghu G, Chang J. Clin Chest Med. 2004;25:621-636, v.
Selman M, et al. Drugs. 2004;64:405-430.
Noninflammatory (multiple hit)
Hypothesis
30. Noninflammatory (multiple hit) Hypothesis
Recurrent
pulmonary
injury
Epithelial/
endothelial
injury and
apoptosis
Loss of basement
membrane
Failure of
re-epithelialization/
re-endothelialization
ECM
deposition
Fibroblast
proliferation
Release of
profibrotic
growth factors
(TGF-b, PDGF,
IGF-1)
Progressive fibrosis with loss of
lung architecture
TGF-b = transforming growth factor-beta
PDGF = platelet derived growth factor
IGF-1 = insulin-like growth factor-1
Noble PW, Homer RJ. Clin Chest Med. 2004;25:749-758, vii.
Raghu G, Chang J. Clin Chest Med. 2004;25:621-636, v. Selman M, et al. Drugs. 2004;64:405-430.
31. • Aberrant vascular remodeling supports fibrosis and may
contribute to increased shunt and hypoxemia
Increased angiogenesis results from imbalance of pro-angiogenic
chemokines (IL-8, ENA-78) and anti-angiogenic, IFN-inducible
chemokines (IP-10)
Vascular remodeling leads to anastomoses between the
systemic/pulmonary microvasculature, increasing right-to-left shunt,
contributing to hypoxemia
Chemokine
imbalance
Increased
angiogenesis
Fibrosis
Noble PW, Homer RJ. Clin Chest Med. 2004;25:749-758, vii.
Strieter RM, et al. Am J Respir Cell Mol Biol. 2003;29(3 suppl):S67-S69.
Vascular Remodeling Hypothesis
Aberrant
vascular
remodeling
32. Defects in Host Defense Mechanisms
May Contribute to Fibrosis
• Defects in endogenous host defense
mechanisms (eg, IFN-g, PGE2 production) that
limit fibrosis after acute lung injury may
contribute to progressive fibrosis
Noble PW, Homer RJ. Clin Chest Med. 2004;25:749-758, vii.
33. NHLBI in an attempt to standardize the diagnostic
criteria used across studies . This committee defined
AEx-IPF as an acute, clinically significant deterioration
of unidentifiable cause and proposed five diagnostic
criteria.
Definition of AEx-IPF
34. 1- Previous or concurrent diagnosis of IPF
2- Unexplained worsening or development of dyspnea within 30
days
3- HRCT with new bilateral ground-glass abnormality and/or
consolidation superimposed on a background reticular or
honeycomb pattern consistent with UIP pattern
4- No evidence of pulmonary infection by endotracheal aspirate
or BAL
5- Exclusion of alternative causes, including:
• Left heart failure
• Pulmonary embolism
• Identifiable cause of acute lung injury.
Diagnostic criteria for AEx-IPF
35. Incidence of AEx-IPF
*American Thoracic Society (ATS), European
Respiratory Society (ERS), Japanese Respiratory
Society (JRS) and Latin American Thoracic Association
(ALAT) on the diagnosis and treatment of IPF state
that AEx- IPF occurs in approximately 5–10% of
patients with diagnosed IPF annually
*A recent retrospective study of data collected from
461 patients with diagnosed IPF found 1-year and 3-
year incidences of AEx-IPF of 14.2% and 20.7%,
respectively .
*However, the incidence rates of AEx-IPF reported in
clinical trials have tended to be lower than this.
36. Pathophysiology of AEx-IPF
A variety of patterns of acute lung injury have been observed in
AEx-IPF . The most common histopathological finding is diffuse
alveolar damage superimposed on the underlying usual
interstitial pneumonia (UIP) pattern , but organizing pneumonia
and extensive fibroblastic foci have also been reported.
Several hypotheses for the etiology of AEx-IPF have been
proposed. AEx-IPF may represent a sudden acceleration of the
underlying disease process due to unknown acute injury to the
lung, or a biologically distinct pathological process due to a
clinically occult condition, such as infection or gastroesophageal
reflux disease (GERD)
37. Pathophysiology of AEx-IPF
As AEx-IPF have a clinical presentation that shares a number of
features with viral respiratory infections (e.g. fever, cough, myalgia), it
has been suggested that occult viral infection may contribute to the
pathophysiology of AEx-IPF.
Several hypotheses for the etiology of AEx-IPF have been proposed.
AEx-IPF may represent a sudden acceleration of the underlying
disease process due to unknown acute injury to the lung, or a
biologically distinct pathological process due to a clinically occult
condition, such as infection or gastroesophageal reflux disease
(GERD).
However, the evidence supporting the involvement of viral
infections in AEx- IPF is mixed .The most recent and extensive
study, which used genomic-based technologies to investigate the
role of viruses in the etiology of AEx-IPF, suggested that viral
infection is not a common cause ofAEx-IPF.
38. Pathophysiology of AEx-IPF
Activation of the immune system, disordered coagulation/fibrinolysis, and oxidative
stress may all contribute to the pathophysiology of AEx-IPF. Immune cells (e.g.
neutrophils, macrophages) ,inflammatory mediators (e.g. interleukin 6, high mobility
group protein B1) ,markers of coagulation/fibrinolysis (e.g. protein C,
thrombomodulin, and plasma activator inhibitor-1) , and markers of oxidative stress
(thioredoxin 1) are all elevated in patients with AEx-IPF.
Epithelial cell damage in patients with IPF is demonstrated by over-expression of
matrix metalloproteinase (MMP)-7, MMP-9 , and Krebs von den Lungen- 6 (KL-6) .
Accelerated epithelial cell proliferation, with increases in the proliferation markers
CCNA2 and Ki-67, in patients with AEx-IPF may be a compensatory response to
injury, and is associated with epithelial cell death. Transforming growth factor (TGF)-
beta, a fibrogenic cytokine, is upregulated in IPF and galectin-3, a mediator of
fibrosis induced by TGF-beta, is elevated in the lungs and serum of patients with
stable IPF and AEx-IPF . Circulating bone marrowderived fibrocytes may also provide
a source of lung fibroblasts and myofibroblasts, as the number of circulating
fibrocytes has been shown to be higher in patients with IPF and AEx-IPF, compared
with healthy subjects
39. Risk factors and precipitating factors for AEx-IPF
*Lower total lung capacity, lower forced vital capacity (FVC)
and/or lower diffusing capacity of the lung for carbon
monoxide (DLco).
*A higher degree of dyspnea (score ≥2 on the modified
Medical Research Council dyspnea scale) or of fibrosis on HRCT
has been shown to increase the risk of AEx-IPF, as has the
presence of concomitant conditions such as emphysema or
pulmonary hypertension.
*Invasive examinations such as bronchoscopy ,
bronchoalveolar lavage (BAL), and pulmonary resection for
lung cancer can precipitate AEx-IPF.
40. Risk factors and precipitating factors for AEx-IPF
*surgical lung biopsy is a precipitating factor for AEx-IPF;
however, the risk of AEx-IPF from video-assisted thoracoscopic
operation appears to be elevated only in patients with severe
physiologic impairment or substantial comorbidity
*In some patients with AEx-IPF, pepsin levels were found to be
elevated in BAL fluid, suggesting a possible role for GERD in
the pathogenesis of AEx-IPF .There is some evidence to
suggest that the treatment of GERD in patients with IPF
reduces mortality rates .
41. Impact of AEx-IPF on patients
*AEx-IPF are certainly a leading cause of hospitalization and
death among patients with IPF. Median survival after an AEx-
IPF has been reported to be between 22 days and 4.2 months.
*There is some evidence that patients with better lung
function (FVC, PaO2, DLCO) prior to AEx-IPF are more likely to
survive an AEx-IPF , suggesting that preservation of lung
function may be an important way of reducing the impact of
AEx-IPF in patients with IPF.
42. Management of AEx-IPF
*The latest international treatment guidelines state that
supportive care remains the mainstay of treatment for AEx-IPF,
but also give a weak recommendation for the treatment of the
majority of patients with AEx-IPF with corticosteroids.
*In clinical practice, the treatment of AEx-IPF is variable.
Corticosteroids (e.g. prednisone, methylprednisolone) are used
in the majority of patients who suffer an AEx-IPF, usually in
pulse doses. Preliminary data suggest that response to high-
dose corticosteroid treatment may depend on the type of HRCT
lesion, with better responses achieved in those with a
peripheral pattern
43. Management of AEx-IPF
*Broad-spectrum antibiotics and immunosuppressants
(cyclosporin or cyclophosphamide) are sometimes used in
addition to corticosteroids .However, the efficacy of
immunosuppressants in the treatment of AEx-IPF is based on a
few small retrospective studies that do not provide conclusive
evidence for benefit.
*Mechanical ventilation is often used in patients with AEx-IPF,
but the data on its effects on outcomes are mixed.
*Other treatments for AEx-IPF that havebeen investigated in
small studies include polymyxin Bimmobilized fiber column
(PMX) hemoperfusion and tacrolimus, a cytokine transcription
inhibitor ,usually administered in addition to corticosteroids.
44. Reducing the risk of exacerbations
*A trial of sildenafil, a phosphodiesterase-5 inhibitor, showed a
numerical reduction in AEx-IPF in patients given sildenafil versus
placebo (3 [3.4%] vs. 7 [7.6%]), but the number of events was
small and the difference was not statistically significant .
*Imatinib, a tyrosine kinase inhibitor , bosentan, an endothelin
receptor antagonist, the anticoagulant warfarin , and inhaled
Nacetylcysteine , numerically higher rates of AEx-IPF were found
in the active treatment arms compared with the placebo arms.
*triple therapy with prednisone, azathioprine,and N-
acetylcysteine in patients with IPF, a significantly higher rate of
AEx-IPF was observed in patients receiving triple therapy versus
placebo
45. Reducing the risk of exacerbations
*Pirfenidone, an anti-fibrotic molecule that has been licensed for the
treatment of IPF in Japan, India, China, Europe, and Canada, but was not
approved in the United States, has shown inconsistent effects on AEx-IPF.
*Nintedanib (formerly known as BIBF 1120) is a tyrosine kinase inhibitor in
clinical development for the treatment of IPF. It reported a lower incidence of
AEx-IPF was observed in patients treated with nintedanib 300 mg/day than
placebo (2.4 vs. 15.7 AEx-IPF per 100 patient years)
*It is interesting that nintedanib may have an effect on AEx-IPF whereas the
tyrosine kinase inhibitor imatinib, which inhibits the platelet-derived growth
factor receptor (PDGFR), did not . Nintedanib is an inhibitor of PDGFR,
vascular endothelial growth factor receptor (VEGFR), and fibroblast growth
factor receptor (FGFR) and this specificity of inhibition may be key to its
effects on AEx-IPF
46. Reducing the risk of exacerbations
*Anti-acid treatment might decrease the frequency of AEx-IPF
by reducing the acidity of the microaspirate .
49. • A 46-year-old man is seen because of 4
months of increasing cough.
• He has HIV infection, his CD4 lymphocyte
count 3 months ago was 240/L (0.24 × 109/L),
and his condition has been stable for several
years while he has been receiving combination
antiretroviral therapy.
• He smokes two packs of cigarettes daily and
stopped using IV drugs 10 years ago.
50. • He denies fever, chills, and night sweats, but
lost 18 lb (8 kg) since the onset of the illness.
Results of a chest radiograph and
representative CT scan images are shown.
51.
52. Which is the most likely diagnosis?
A. Pneumocystis jiroveci pneumonia.
B. Kaposi sarcoma.
C. Aspergillosis.
D. Adenocarcinoma
53. • The radiograph shows an abnormal opacity in
the lingula and enlargement of the left hilum,
and the CT scan images show mass lesions in
the lingula, hilum, and mediastinum, with
encasement of the left upper lobe bronchus.
These findings are most consistent with
advanced lung cancer (choice D is correct).
54. • Although Kaposi sarcoma, non-Hodgkin
lymphoma, and cervical cancer are recognized
as AIDS-defining diseases in people who are
HIV-seropositive.
• The incidence of lung cancer is now
recognized to be increased in people with HIV
infection, especially in the years following the
use of combination antiretroviral therapy as
the standard of care.
55. • Although most people with HIV infection are
current or former smokers, their risk of
developing lung cancer appears to be
increased, even when incidence ratios are
adjusted for smoking.
• The prevalence of microsatellite alternations
reflecting genomic instability also occurs with
greatly increased frequency in HIV-associated
lung cancers, possibly playing a role in their
pathogenesis
56. • Patients with lung cancer in the setting of HIV infection
tend to be relatively young at presentation (mean age,
45 years) and have mild or moderate
immunosuppression.
• Similar to age-matched control subjects, 75% to 90%
present with stage III or IV disease. Adenocarcinoma is
the most common histologic type, and the prognosis
appears to be worse in patients with HIV infection.
• Until further studies are performed, the diagnostic and
therapeutic approaches to HIV-associated lung cancer
are the same as for other patients, although the
efficacy and toxicity of chemotherapy and radiotherapy
may be different.
57. • Until further studies are performed, the
diagnostic and therapeutic approaches to HIV-
associated lung cancer are the same as for
other patients, although the efficacy and
toxicity of chemotherapy and radiotherapy
may be different.
58. • Pneumocystis pneumonia is the most common
opportunistic infection in patients with HIV
infection but would not be expected to
present with lung and mediastinal masses or
in a patient with a CD4 lymphocyte count
200/mL ( 0.200 × 109/L)
(choice A is incorrect).
59. • Kaposi sarcoma may appear with multiple
pulmonary nodules, pleural effusions, and
intrathoracic lymphadenopathy, but this
pattern of a single large lung mass with
unilateral lymphadenopathy would be
distinctly unusual with this neoplasm
(choice B is incorrect).
60. • Invasive pulmonary aspergillosis occurs in
patients with HIV infection but usually
appears with invasive and cavitary disease,
without hilar and mediastinal
lymphadenopathy, and only in the setting of
severe immunosuppression (CD4 lymphocyte
count usually 50/mL [ 0.050 × 109/L])
(choice C is incorrect).
61. Which is the most likely diagnosis?
A. Pneumocystis jiroveci pneumonia.
B. Kaposi sarcoma.
C. Aspergillosis.
D. Adenocarcinoma
63. • A 29-year-old man with a 2 pack-year smoking
history is referred for evaluation of an
abnormal chest radiograph.
64. • The patient had a prolonged hospital
admission 9 months ago for traumatic injuries
related to a car accident.
• A representative chest radiograph early in that
hospitalization
65. • He suffered traumatic brain injury that left
him unable to communicate and wheelchair-
bound but able to move all four extremities.
The patient’s past history is notable for
community-acquired pneumonia 4 weeks
prior to the car accident, for which he was
treated as an outpatient.
66. • Several CT scans have been performed over
the last 5 months, with the most recent noting
that the lesion in question has increased in
size from 5.6 × 4 cm to 7.3 × 5 cm over the 2-
month interval.
67.
68. • The patient’s mother notes that he currently
has no discernible respiratory signs other than
an occasional nonproductive cough. Results of
an examination of his lungs are normal. Which
of the following is the most appropriate next
step?
A. Transthoracic needle biopsy.
B. Bronchoscopy with biopsy.
C. Surgical biopsy.
D. Observation
69. • The patient has a traumatic rupture of the
right hemidiaphragm with herniation of the
liver into the right chest cavity.
• Continued observation is the most
appropriate current choice, given the patient’s
lack of symptoms and a clear diagnosis of liver
herniation made by chest CT scan (choice D is
correct).
70. • Given a clear diagnosis, no invasive diagnostic
procedures are required (choices A, B, and C
are incorrect).
A. Transthoracic needle biopsy.
B. Bronchoscopy with biopsy.
C. Surgical biopsy.
71. • In this patient, the increasing size of the lesion
indicates gradual entrance of the liver though
a right hemidiaphragm defect driven by the
pleuroperitoneal pressure gradient. The CT
scan indicates that the enlarging chest lesion
is liver, as supported by very similar
Hounsfield units (density) of the “chest” lesion
and the liver, and the contiguous nature of the
chest lesion and the liver
72. • Right-sided hemidiaphragm ruptures/tears are
less frequently accompanied by herniated
viscera than are left-sided ruptures.
• The viscera most commonly herniated are the
liver, as in this patient, and, occasionally, the
colon.
• Right sided hemidiaphragm trauma-related
tears (defects) are eight times less common
than left-sided tears, likely due to the
protective effect afforded to the right
hemidiaphragm by the liver.
73. • Blunt trauma due to motor vehicle accidents is
the most common cause of traumatic closed
rupture of either hemidiaphragm, as was the
case with this patient.
• When the diagnosis of right-sided rupture is
not made immediately, diagnosis can be
delayed from weeks, as in this patient, to
years.
74. • With left-sided traumatic diaphragmatic rupture,
herniation of the stomach, spleen, large bowel,
liver, small intestines, and omentum is common.
• Intrathoracic splenosis and spread of splenic
tissue to the chest cavity can occur after
traumatic injuries to the spleen.
• Nonsurgical diagnosis of traumatic diaphragmatic
herniation can often be made by plain chest
radiograph.
• CT scan or MRI imaging may be needed to
confirm herniation
76. • A 54-year-old woman was referred for assessment of neck
swelling. She went to her family physician a few weeks ago
and was diagnosed with hypertension. She started
receiving indapamide.
• Shortly thereafter, she noted swelling on the right side of
her neck and a rash over the anterior chest. She saw her
family physician who noted swelling on the right side of her
neck.
• He arranged a chest radiograph followed by a CT scan of
the neck and chest. She had a 30 pack-year smoking
history. She had no other medical problems. Results of a
physical examination were negative other than the neck
swelling.
77.
78.
79.
80. At this point, what would you do?
• A. Start low-molecular-weight heparin.
• B. Arrange early radiotherapy.
• C. Discontinue indapamide.
• D. Arrange urgent chemotherapy.
81. • The chest radiograph demonstrates a right
lung mass. The CT scan shows a 3.0 × 2.5-cm
mass in the posterior segment of the right
upper lobe and a 2.9 × 2.0-cm right hilar
lymph node.
• The right internal jugular vein reveals
thrombosis, with edema surrounding it. The
thrombus extends inferiorly to the right
brachiocephalic vein, but the superior vena
cava is patent. Ultimately, the patient was
shown to have non-small cell lung cancer.
This patient, therefore, has a malignancy
with internal jugular vein thrombosis (IJVT).
82. What is the next step?
• A. Start low-molecular-weight heparin.
• B. Arrange early radiotherapy.
• C. Discontinue indapamide.
• D. Arrange urgent chemotherapy.
83. • Early radiotherapy would be appropriate if the patient had
a superior vena cava obstruction, but that is not the case
(choice B is incorrect).
• Discontinuing indapamide would be appropriate if the neck
swelling and rash were thought to be due to an allergic
reaction. However, the swelling and “rash,” related to
collateral blood supply, were secondary to the jugular vein
thrombosis (choice C is incorrect).
• An oncology consult should be scheduled, but the
administration of chemotherapy should be delayed until a
tissue diagnosis is obtained. Chemotherapy is not urgently
required in this clinical setting (choice D is incorrect).
85. • A healthy, active 82-year-old woman who regularly hikes at 14,000-ft
(4,200-m) elevation develops a urinary tract infection, for which she is
treated with nitrofurantoin. Within 3 days, she develops acute respiratory
insufficiency requiring emergent intubation and mechanical ventilation
support.
• After a thorough evaluation, she was diagnosed with acute nitrofurantoin
pulmonary toxicity and empirically treated with IV corticosteroids with
symptomatic improvement and extubation after 10 days.
• After completing a 4-week taper of oral corticosteroids, she develops
progressive breathlessness, without exertional hypoxia, while walking 500
to 1,000 ft (150 to 300 m).
• Follow-up CT imaging of the chest demonstrated resolution of the
previously identified ground-glass opacities without residual parenchymal
abnormalities. Spirometry was recently performed.
• In addition to breathlessness, she notes significant anxiety when walking,
with a globus sensation and inability to get a satisfying breath.
86.
87. The next most appropriate
intervention for the patient would be?
• A. PET scan.
• B. CT angiography.
• C. Cardiopulmonary exercise testing.
• D. Fiberoptic laryngoscopy.
89. • Laryngotracheal stenosis, when associated with a prior
injury such as intubation, manifests with symptoms 2 to 4
weeks following the initial injury. Dyspnea, air hunger,
hoarseness, stridor, dysphagia, or recurrent aspiration may
occur. Signs of a fixed lesion on flow-volume loop may be
present in patients with severe disease. Confirmation by
direct laryngoscopy and bronchoscopy is required (choice D
is correct).
• Anterior glottic scarring is often extensive, involving the
true vocal cords and false cords, and often is the result of
unmanaged severe external laryngeal trauma. Posterior
glottic stenosis is typically a manifestation of endotracheal
tube injury. CT imaging is complimentary in preoperatively
evaluating patients but is limited in grading the severity of
the stenosis. Functional abnormalities of the vocal folds,
termed vocal cord dysfunction, may occur after intubation
and manifest with a globus sensation and paroxysmal
dyspnea.
90. • In the absence of a concern for primary or metastatic
laryngeal obstruction, PET scan imaging has limited
value in the evaluation of patients with laryngeal
stenosis. Given this patient’s presentation, malignancy
is not a primary concern (choice A is incorrect).
• CT angiography and cardiopulmonary exercise testing
are important modalities in the evaluation of patients
with dyspnea. Given the abnormalities on the patient’s
flow-volume curve, thromboembolic disease and
progressive parenchymal involvement from the
nitrofurantoin pulmonary toxicity are less likely
(choices B and C are incorrect).
91. The next most appropriate
intervention for the patient would be?
• A. PET scan.
• B. CT angiography.
• C. Cardiopulmonary exercise testing.
• D. Fiberoptic laryngoscopy.
93. • A 27-year-old woman, gravida 2, para 1, at 35 weeks of
gestation, has dyspnea on exertion. She has had some
element of dyspnea on exertion since late in her first
trimester of pregnancy but feels that it has worsened since a
car trip of approximately 2½ h in each direction. She now feels
“winded” climbing the single flight of stairs in her house. She
also has some discomfort in her right anterior lower chest
with deep inspiration, which is new since the trip. She is still
able to complete all of her daily activities and denies cough,
wheeze, fever, or hemoptysis. There is no leg swelling or pain.
Her past medical history is unremarkable, and she had no
difficulties with her first pregnancy. There is no personal or
family history of VTE. Her only medication is prenatal vitamin
pills and she does not smoke. She reports no allergies.
94. • On physical examination, she is in mild respiratory distress at rest.
BP is 96/52 mm Hg, heart rate is 102/min, respiratory rate is
20/min, and temperature is 37.1C, orally. Oxygen saturation is 95%
at rest, and falls to 91% with ambulation of approximately 200 ft
(60 m). No jugular venous distension is present, and there is no
chest wall tenderness at the right-side site of her chest where she
has pain with inspiration. Breath sounds are normal, and no
adventitious sounds are appreciated. Cardiac examination reveals
tachycardia with regular rate and rhythm, and without rubs,
murmurs, or gallops appreciated. Her abdomen is normal for
gestational age, and there is no lower extremity edema. A chest
radiograph performed with shielding shows some atelectasis at the
right base, and lower extremity ultrasonography shows no evidence
of DVT. The physician remains concerned about the possibility of
pulmonary embolism and wishes to pursue the diagnosis further.
95. Which diagnostic test is most appropriate at this
point?
• A. CT scan of the chest with contrast.
• B. Measurement of plasma D-dimer
concentration.
• C. Transesophageal echocardiography.
• D. V / Q scanning.
96. • This patient has worsened subjective dyspnea, pleuritic chest pain,
and exertional desaturation in a clinical setting, which could
indicate pulmonary embolism (ie, occurring during the third
trimester of pregnancy and following a period of relative
immobilization for her automobile trip).
• Dyspnea is very commonly experienced during pregnancy. This
physiologic “dyspnea of pregnancy” appears due, in large part, to
elevated concentrations of progesterone directly stimulating CNS
respiratory centers to produce hyperventilation. This tends to
develop early in the course of pregnancy and is not associated with
chest pain or desaturation. In contrast, the risk for VTE
progressively increases during pregnancy, peaking in the third
trimester and the postpartum period. Because of the timing,
setting, and associated features of her presentation, evaluation for
VTE is warranted.
• A chest CT scan with contrast is the diagnostic study of choice for
patients with a high pretest probability of pulmonary embolism,
such as this patient, or for patients who have an elevated plasma D-
dimer concentration on initial testing.
97. • A normal D-dimer concentration measured by a validated
enzyme-linked immunosorbent assay (ELISA) method
effectively excludes the diagnosis in a hemodynamically
stable outpatient with low or intermediate clinical
probability.
• However, the D-dimer assay is of limited value in patients
with a high pretest probability of pulmonary embolism, and
has reduced specificity in pregnant patients, hospitalized
patients, individuals with cancer, and the elderly. In this
• patient, the already high pretest probability and the low
specificity of the D-dimer assay during pregnancy render
the D-dimer test unhelpful.
98. • V/Q scanning is a reasonable alternative in institutions that do not
have adequate experience in the use of CT imaging in pulmonary
embolism. However, V/Q scanning is diagnostic in only 30% to 50%
of patients with suspected pulmonary embolism, and the
remainder need to be followed up with additional studies. In
addition, while the maternal radiation dose of V/Q scanning is less
than CT scanning, the fetal radiation dose can actually be higher.
The greatest utility of V/Q imaging generally is among patients with
a low pretest probability of pulmonary embolism and a normal
chest radiograph. In such a setting, a normal or near normal
perfusion scan is generally sufficient to exclude the diagnosis;
however, this patient had right lower lobe atelectasis, making a
definitive study unlikely. For all of these reasons, V/Q imaging is
undesirable in this patient. If the chest radiograph findings were
normal in the patient, a perfusion scan would have been useful in
excluding pulmonary embolism if it returned as normal or near
normal.
99. • In hemodynamically unstable patients in whom pulmonary
embolism is suspected, echocardiography can presumptively
establish the diagnosis by demonstrating right-sided heart strain
(visible via transthoracic or transesophageal techniques) and/or by
demonstrating emboli in the main pulmonary arteries (generally
only visible via transesophageal studies). Echocardiography offers
the advantage of being a bedside procedure that can be performed
and interpreted quickly in patients who are too ill to permit
transport, and it does not require either ionizing radiation or
contrast material. However, it is unlikely to be diagnostic in this
hemodynamically stable patient.
• MRI is an attractive option because it does not use ionizing
radiation to generate images. To date, no health risks have been
associated with MRI, although experience with its use in pregnancy
is not extensive. Unfortunately, the utility of MRI to diagnose
pulmonary embolism is limited by insufficient sensitivity and a high
rate of technically inadequate images.
100. Which diagnostic test is most appropriate at this
point?
• A. CT scan of the chest with contrast.
• B. Measurement of plasma D-dimer
concentration.
• C. Transesophageal echocardiography.
• D. V / Q scanning.
