Other Lung Diseases

Mark J. Rosen, MD, FCCP

Director, Global Education and Strategic Development
American College of Chest Physicians
Professor of Medicine
Hofstra University North Shore-LIJ
School of Medicine
Cb[ecnves
AL Lhe end of Lhls sesslon, paruclpanLs wlll be able Lo:
1. uescrlbe Lhe pulmonary compllcauons of slckle
cell anemla
2. ulscuss pulmonary dlsorders assoclaLed wlLh
clrrhosls
3. LlsL and descrlbe pulmonary compllcauons of Plv
lnfecuon
PULMONARY COMPLICATIONS
OF SICKLE CELL DISEASE
Gladwin MT, Vichinsky E
N Engl J Med 2008;359:2254-2265
S|ck|e Ce|| nemog|ob|nopath|es
Slckle cell anemla (hemoglobln SS) aecLs 1/630
Afrlcan-Amerlcans
ln Lhe uS, also aecLs Launos from Lhe Carlbbean,
CenLral Amerlca, SouLh Amerlca
S|ck|e Ce|| D|sease
Pothoqenesis
Bunn HF. N Engl J Med
1997; 337:762-769
Lonergan G J et al. Radiographics 2001;21:971-994
2001 by Radiological Society of North America
Sickle Cell Disease
Pathogenesis
Platt OS. N Engl J Med
2000;342:1904-7
S|ck|e Ce|| Anem|a
nemoq/obin po/ymeritonon
ueoxygenauon: degree and durauon
Pemoglobln concenLrauon ln 88C: cellular
dehydrauon
lnversely proporuonal Lo hemoglobln l
S|ck|e Ce|| D|sease
Pothoqenesis
Mlcrovascular occlosloo
AJbesloo of 88Cs and W8Cs Lo vascular endoLhellum
vosocoosttlcuoo: endoLhelln-1 expressed aer
conLacL wlLh slckled 88Cs
Acuvouoo of cooqolouoo sysLem: LhrombocyLosls,
procoagulanL 88C llplds
NO Jysteqolouoo followlng release of arglnlne and
Pgb from hemolysls
Sickle Cell Disease
Role of NO
Hemolysis
Release free hemoglobin

Scavenge NO
Release RBC arginase

SLeudel W. AnesLheslology
1999,91:1090-121
CrlmLhs. !u. n Lngl ! Med
2003,333:2683-2693

S|ck|e-Ce|| D|sease
Pu/monory syndromes
AcuLe chesL syndrome (ACS)
laL embollsm syndrome
Chronlc resLrlcuve lung dlsease
ulmonary arLerlal hyperLenslon
CPC. N Engl J Med
S|ck|e-Ce|| D|sease
4cute chest 5yndrome
Looks llke pneumonla: chesL paln, fever, cough,
oen durlng palnful crlsls
Cx8: mululobe or lower lobe opaclues, pleural
euslon (13)
MosL common cause of deaLh ln adulLs wlLh slckle
cell dlsease
Acute Chest Syndrome
Pothoqenesis
ulmonary lnfarcuon
laL embollsm
lo slto Lhrombosls
1hromboembollsm
1horaclc bone lnfarcuon paln aLelecLasls and
pneumonla
lnfecuon
Gladwin M, Vichinsky E. N Engl J Med 2008;359:2254-2265
Acute Chest Syndrome
1he most common pathogen |dennhed
|n panents w|th acute chest syndrome
|s:
A. 5. poeomooloe
8. n. lofoeozoe
C. c. poeomooloe
u. lnuenza vlrus
1
Acute Chest Syndrome
couses ond Outcomes
671 eplsodes ln 338 pauenLs
Comprehenslve dlagnosuc evaluauon
8lood culLures
nasopharyngeal culLures
8ronchoscopy: culLures, faL sLalns
C8 for cblomyJlo
AcuLe and convalescenL sera: mycoplasma, L8
vlrus, cblomyJlo, parvovlrus
Vichinsky EP et al. N Engl J Med 2000;342:1855-65.
Acute Chest Syndrome
Etiology
4
25
30
43
44
48
59
0 10 20 30 40 50 60 70
Legionella
Mixed inf
Bacteria
Virus
Mycoplasma
Chlamydia
Fat embolism
*Established in 364/670 episodes
Vichinsky EP et al. N Engl J Med 2000;342:1855-65
ACS |n anents > 20 years
22 requlred mechanlcal venulauon
redlcLors: > 4 lobes lnvolved, plaLeleLs < 200,000,
hlsLory of cardlac dlsease
9 dled
Vichinsky EP et al. N Engl J Med 2000;342:1855-65.
Cerebral infarct in a 19-year-old patient with Sickle Cell Anemia
Lonergan G J et al. Radiographics
2001;21:971-994
2001 by Radiological Society of North America
Acute Chest Syndrome
Neotoloqlc compllcouoos
22 of adulLs developed neurologlc dlsorders
AlLered menLal sLaLus
Selzures
neuromuscular
Anoxlc ln[ury
Pemorrhage
lnfarcuon
Vichinsky EP et al. N Engl J Med 2000;342:1855-65.
Acute Chest Syndrome
1teotmeot
88C Lransfuslon
Analgeslcs
Pydrauon
Cxygen
Anubloucs
lncenuve splromeLry (!)
Acute Chest Syndrome
New 1teotmeots?
nC: oot e[ecuve ln ume Lo resoluuon of crlsls
SLem cell LransplanLauon
Cene Lherapy
Gladwin MT, et al. JAMA 2011;305:893-902
Iat Lmbo||zanon Syndrome
MosL common posLparLum
Mululobar opaclues or A8uS
neurologlc
8enal fallure
eLechlae
laL globules ln spuLum and urlne
osluve bone scans
1he most |mportant pred|ctor of chron|c
restr|cnve |ung d|sease |n s|ck|e ce|| d|sease |s:
A. 8lood hemoglobln level
8. number of eplsodes of acuLe chesL syndrome
C. PlsLory of clgareue smoklng
u. Pemoglobln SC genoLype
3
Pulmonary Hypertension in Sickle Cell
Disease
Gladwin MT, et al. N Engl J Med 2004;350:886-895
u|monary nypertens|on |n S|ck|e Ce||
D|sease
193 adulLs wlLh slckle cell dlsease
uoppler-dened AP ln 32, 6 on rlghL hearL
caLheLerlzauon
AssoclaLed wlLh
rlor cardlovascular, renal compllcauons
Plgh LuP (hemolysls?)
Plgh alkallne phosphaLase
Low Lransferrln levels
lncreased rlsk of deaLh (raLe rauo 10.1)
Gladwin MT, et al. N Engl J Med 2004;350:886-895
Parent F, et al. N Engl J Med 2011;365:44-53
u|monary nypertens|on |n S|ck|e Ce|| D|sease
Gladwin MT, et al. N Engl J Med 2004;350:886-895
u|monary nypertens|on |n S|ck|e Ce||
D|sease
Many false-posluve echocardlograms compared wlLh
rlghL hearL caLheLerlzauon
auenLs wlLh AP more llkely Lo be
Clder
oorer funcuonal sLaLus
Plgher levels of n-Lermlnal pro-braln naLrlureuc
pepude
Parent F, et al. N Engl J Med 2011;365:44-53
L|ver-Lung Syndromes
PepaLopulmonary syndrome
orLopulmonary hyperLenslon
Alpha-1 anuLrypsln declency
Pepauc hydroLhorax
HEPATOPULMONARY
SYNDROME
Rodriguez-Roisen R, Krowka MJ
N Engl J Med 2008;358:2378-87
nepatopu|monary Syndrome
1rlad: llver dlsease, hypoxemla, lnLrapulmonary
vascular dllaLauons (precaplllary and caplllary)
Slgns: uyspnea, splders, clubblng, hypoxemla
uluslon-perfuslon dlsorder
Plgh cardlac ouLpuL
AnaLomlc shunLs: pleural splder nevl and
porLopulmonary anasLamoses (plaLypnea)

Rodrguez-Roisin R, N Engl J Med 2008;358:2378-2387
Rodrguez-Roisin R, N Engl J Med 2008;358:2378-2387
nepatopu|monary Syndrome
aLhogenesls of vascular dllaLauons: abnormal
vascular medlaLors leavlng Lhe llver enLer Lhe
lungs remodel pulmonary vessels
lncreased nC producuon vasodllauon, CC
nepatopu|monary Syndrome
uloqoosls
Cllnlcal: llver dlsease (13-20 of pauenLs wlLh
clrrhosls have PS)
CrlLerla:
orLal hyperLenslon
A-a uC
2
>13 mm Pg
vascular dllaLauons
Lchocardlographlc: alr bubbles appear ln le aLrlum
3-6 beaLs aer vlsuallzauon ln rlghL aLrlum, ot
nuclear: 8adlonuclelde appears ln braln 4-6 cycles
aer ln[ecuon
Wh|ch of the fo||ow|ng |s most ||ke|y to
|mprove hypoxem|a |n the hepatopu|monary
syndrome?
A. Assumlng an uprlghL posLure
8. AdmlnlsLer supplemenLal C
2
C. AdmlnlsLer dlluazem
u. Llver LransplanLauon
4
nepatopu|monary Syndrome
1teotmeot
Long-Lerm oxygen, buL may noL work
urugs have noL worked
Llver LransplanLauon ls Lhe besL LreaLmenL
PS assoclaLed wlLh lncreased perloperauve
morLallLy
aC
2
<60 mm Pg ls consldered an lndlcauon for
LransplanLauon, hlgher prlorlLy
ortopu|monary nypertens|on
Cccurs ln 1-2 of pauenLs wlLh clrrhosls and porLal
hyperLenslon
lndlsungulshable from lAP
May noL lmprove aer llver LransplanLauon
nepanc nydrothorax
ulmculL-Lo-conLrol pleural euslons ln pauenLs wlLh
asclLes
robably due Lo congenlLal anaLomlc defecLs ln Lhe
dlaphragm
leural uld almosL ldenucal wlLh asclLes
usually LransudaLe, rlghL>le
Lmpyema may occur ln pauenLs wlLh perlLonlus
nepanc nydrothorax
1teotmeot ls Jl[colt
1horacenLesls: uld reaccumulaLes
ChesL Lube: volume and elecLrolyLe depleuon
leurodesls: usually unsuccessful
Surglcal repalr of dlaphragm: few cenLers have
experlence
erlLoneovenous shunLs: leural uld pressure <
venous pressure
nepanc nydrothorax
1teotmeots
1rans[ugular lnLrahepauc porLosysLemlc shunL
Llver LransplanLauon
4.7
4.2
4.0
3.7
5.0
16.2
5.3
6
0
2
4
6
8
10
12
14
16
18
1995 1997 1999 2001 2003 2005 2006 2007
http://www.cdc.gov/nchs/data/nvsr/nvsr58/nvsr58_01.pdf
Annual Number of AIDS Deaths in the U.S.
Dec||ne |n nIV]AIDS Death kates
D
e
a
t
h
s

P
e
r

1
0
0
,
0
0
0

P
o
p
u
l
a
t
i
o
n

A81
avallable
Lect of Ak1 on Inc|dence of CI
Morris A, et al. Emerg Inf Dis Oct 2004 http://www.cdc.gov/ncidod/EID
nIV: kad|ograph|c auerns
local Medlasunal Ln
bacLerla, 18, C 18, MAC, kS, fungl
lymphoma

uluse leural Luslon
C, 18, bacLerla, bacLerla, 18, kS,
fungl, CMv, kS oncouc, CPl, fungl
lymphoma (LL)

uluse nodules Cavlues
18 (mlllary), kS (large), 18 (hlgh Cu4+),
fungl (small) C, k. epol, NocotJlo
1he hnd|ng that best pred|cts that a
symptomanc panent does not have C
|s:
A. normal chesL radlograph
8. lnduced spuLum LhaL shows no organlsms
C. Cu4+ cell counL = 400 cells/L

u. aC
2
= 83 mmPg
2
A 33 year-o|d nIV+ ma|e IDU presents w|th cough,
dyspnea, and fever. SpC
2
|s 8S on room a|r, and Ckk
shows d|use opac|nes. 1M-SM2 and corncostero|ds
are ordered. Induced sputum shows no pathogens.
What wou|d you do next?
A. Cbserve for ve days, furLher Lesung only lf he
deLerloraLes
8. 8ronchoscopy wlLh 8AL
C. 8ronchoscopy wlLh 8AL ooJ 188
u. C1 scan of chesL
3
Pseudomonos |n nIV
Predisposinq foctors
Advanced lmmunosuppresslon
Long-Lerm lv caLheLers
Long-Lerm anubloucs
8epeaLed hosplLallzauons
lmmunosuppresslve LreaLmenLs


Cytomega|ov|rus pneumon|a |n panents
w|th AIDS |s:
A. usually found ln drug users
8. ulagnosed by serologlc Lechnlques
C. ulagnosed by culLure of 8AL uld
u. ulagnosed by hlsLology or cyLology
6
Invas|ve pu|monary asperg|||os|s |n
nIV
Cases were more llke Lhan conLrols Lo have:
neuLrophll counL < 1,000/mL
Cu4+ counL < 30/mL
used corucosLerolds
rlor C
ueaLh durlng sLudy (90, 21)
Wallace !M, eL al. ChesL 1998, 114:131-137
Non|nfecnous D|sorders
Neop/osnc
kaposls sarcoma
Lymphoma
usually 8-cell
rlmary euslonal lymphoma: llquld
lymphoma, assoclaLed wlLh PPv-8, poor
prognosls
Lung cancer (adenocarclnoma)
A|| of the fo||ow|ng are character|snc
rad|ograph|c hnd|ngs |n thorac|c kapos|s
sarcoma, except:
A. leural euslon
8. Medlasunal lymphadenopaLhy
C. kerley 8 llnes
u. neumoLhorax
7
kapos| Sarcoma
Non|nfecnous D|sorders |n nIV
Lmphysema
Alrway dlsease
ulmonary hyperLenslon
Lung Cancer
lmmune reconsuLuuon
nl, Ll, CC
Non|nfecnous D|sorders |n nIV
Pu/monory 4rterio/ nypertension
Looks llke lAP
1/200 cases of Plv lnfecuon
noL relaLed Lo Plv lnfecuon of pulmonary vascular
endoLhellum
unrelaLed Lo Cu4+ counL
1reaL llke lAP
rognosls generally poor

45-year-old IDU is admitted with fever, weight loss,
and a RLL opacity.
Sputum AFB smear +, RIPE started.
HIV+, ART is started.
Improves, discharged on DOT, returns two weeks
later with fever. He is otherwise well.
The CXR shows new mediastinal
lymphadenopathy and a right pleural effusion.
What |s the most appropr|ate step at th|s
nme?
A. 8ronchoscopy wlLh 8AL and 18nA of Lhe
medlasunal lymph nodes
8. Add sLrepLomycln and clprooxacln
C. SLop A81
u. Cbservauon
8
Immune kestoranon Syndromes
CMv: reunlus, uvelus, vlLrlus, collus, pancreauus
MAC: lymphadenlus, Addlsons, skln nodules
Pepauus C vlrus: acuLe hepauus, clrrhosls wlLh
lncreased PCv 8nA
aradoxlcal worsenlng of 18, C, sarcoldosls (?)
Sarco|dos|s-||ke u|monary D|sorder
aher Ak1
Naccache JM, et al. AJRCCM 1999;159:2009-2013
Sarcoidosis-like Pulmonary Disorder
after ART
Naccache JM, et al. AJRCCM 1999;159:2009-2013
H&E CD8+ CD4+
Cr|nca| Care |n nIV Infecnon
CpporLunlsuc lnfecuons less common
More common:
8acLerlal pneumonla
Sepsls
Llver dlsease (P8v and PCv)
kldney dlsease
1hlngs LhaL Plv-negauve people geL