Los|noph|||c Þneumon|as

SLephanle M. Levlne Mu, lCCÞ

unlverslLy of 1exas PealLh Sclence CenLer-
San AnLonlo
Iacu|ty D|sc|osures

no relauonshlps exlsL wlLh lndusLry ne
Learn|ng Cb[ecnves
1o revlew Lhe ma[or eoslnophlllc pulmonary
dlsorders
1o be able Lo dlsungulsh acuLe and chronlc
eoslnophlllc pneumonla
1o be famlllar wlLh common presenLauons of ALÞ,
CLÞ, Allerglc 8ronchopulmonary Asperglllosls (A8ÞA),
Loslnophlllc CranulomaLosls wlLh Þolyangllus,
(Churg- SLrauss Syndrome), Pypereoslnophlllc
Syndrome
CyLoklnes LhaL sumulaLe growLh, dlñerenuauon, and
producuon of eoslnophlls: lL-3, lL-3, CM-CSl.
Cnly lL-3 ls speclñc for eoslnophlls
Cranules conLaln:
-M8Þ (ma[or baslc
proLeln)
-Loslnophlllc cauonlc
proLeln
-Loslnophll derlved
neuroLoxln
-CharcoL-Leyden
crysLal proLeln

Dehn|non
A heLerogeneous group of dlsorders characLerlzed by
lncreased numbers of eoslnophlls ln 1 or more
comparLmenLs of Lhe lung and/or blood
8adlographlc abnormallues
lmpalred pulmonary funcuon
+/- perlpheral eoslnophllla
1he role of Lhe eoslnophll ln many of Lhese dlseases
dlñers and ls noL well characLerlzed
– Cood guy vs bad guy vs bysLander
C|ass|hcanon- based on anatom|ca|
|ocanon
Alrway
AsLhma
Loslnophlllc bronchlus
Allerglc bronchopulmonary asperglllosls
8ronchocenLrlc granulomaLosls
Þarenchyma- known cause (secondary) vs ldlopaLhlc
(prlmary)
Þr|mary Los|noph|||c D|sorders
Lung llmlLed
Slmple pulmonary eoslnophllla
AcuLe eoslnophlllc pneumonla
Chronlc eoslnophlllc pneumonla
SysLemlc
Pypereoslnophlllc syndrome
Loslnophlllc CranulomaLosls wlLh Þolyangllus (Churg-
SLrauss Syndrome)
Secondary Los|noph|||c D|sorders
Alrway cenLered
– Allerglc bronchopulmonary asperglllosls
lnfecuons- paraslLes, bacLerlal, fungal (asperglllus,
coccldloldes)
vasculludes
urugs/1oxlns
Mallgnancy- lymphoma, lung cancer, leukemla, MuS
lLu- PÞ, LCP, CCÞ, sarcoldosls
Ç 1- Case
47 yo female wlLh hlsLory of well conLrolled asLhma
on lnhaled CS x 10 years
Worsenlng cough and wheezlng x 2 monLhs
Cough producuve of Lhlck whlLe spuLum
no fevers, chllls, welghL loss
ÞL- scauered wheezes
Labs- lgL mlldly elevaLed, 20° eoslnophlls on C8C
Cx8 - ? nodule
Ç 1- Case
Ç 1- Case
Ç1- What |s the ||ke|y d|agnos|s |n th|s
case?
A. 8ronchogenlc carclnoma
8. Carclnold
C. Allerglc bronchopulmonary asperglllosls
u. lorelgn body asplrauon
A||erg|c 8ronchopu|monary Asperg|||os|s
(A8ÞA) or A||erg|c 8ronchopu|monary
Mycos|s
PypersensluvlLy Lo lnhaled fungal anugens
usually buL noL always asperglllus ( A fomlqotos)
2-14° of asLhmaucs- older
1-13° of Cysuc llbrosls pauenLs- male, lower lung
funcuon
Þroc Am 1horac Soc 7:237, 2010
A8ÞA- D|agnos|s
AsLhma*
Þosluve lmmedlaLe hypersensluvlLy skln LesL Lo
Asperglllus*
Serum preclpluns Lo Asperglllus*
lgL > 1000ng/ml*
LlevaLed serum anu Al lgL and lgC*
Þulmonary opaclues
Loslnophllla
+/- Þroxlmal bronchlecLasls
Mucous plugs wlLh Asperglllus
uual cuLaneous reacuon Lo Asperglllus
Ma[or
M|nor
A8ÞA- Stages
SLage l- AcuLe- elevaLed lgL, asLhma, eoslnophllla,
opaclues, preclplLaung anubody
SLage ll- 8emlsslon- sympLom resoluuon, reduced lgL
SLage lll- Lxacerbauon- lncreased lgL and sympLom
recurrence
SLage lv- SLerold dependenL asLhma- elevaLed lgL
SLage v- llbrouc lung dlsease
A8ÞA- kad|ograph
1ranslenL opaclues
upper lobe predomlnanL
llnger ln glove
Mucold lmpacuon
Þroxlmal/ CenLral bronchlecLasls
A8ÞA
ÞaLhology- mucold lmpacuon, bronchocenLrlc
lnßammauon wlLh eoslnophlls, lymphocyLes, plasma
cells
lmmunologlc
1reaLmenL-
– corucosLerolds
– +/- lLraconazole
– sLandard asLhma LreaLmenL
– lnhaled corucosLerolds ?
– llmlLed evldence for omallzumab
Loemer Syndrome
Slmple pulmonary eoslnophllla
Causes- paraslLes (Ascarls, ulroñlarla), drugs,
ldlopaLhlc
lever, cough, dyspnea, rare hemopLysls
Þerlpheral eoslnophllla
Cx8- ßeeung opaclues
ÞaLhology- eoslnophlllc lnñlLraLes
1reaLmenL- self llmlLed, rarely need sLerolds
Þaras|nc Infecnons
Ascarls
SLrongyloldes
ulroñlarla
Lchlnococcus
Wucherla
SchlsLosoma
1oxocara
ulrecL lnvaslon or lmmunologlc reacuon
Cl sympLoms
Þulmonary sympLoms- cough, wheezlng
1rop|ca| Þu|monary
Los|noph|||a
Ceographlc- endemlc Lo lndla, Afrlca, SL Asla
lllarlal relaLed- wocbetetlo booctofl
nocLurnal cough*, fevers, welghL loss, malalse,
dyspnea, wheezlng, chesL paln
8efracLory asLhma
Cardlac and CnS lnvolvemenL - rare
Þerlpheral eoslnophllla, elevaLed lgL
8AL- eoslnophllla
1reaLmenL- dleLhylcarbamazlne
Strongy|o|des
AuLolnfecuon
lmmunocompromlsed hosL
Cough, wheezlng, hemopLysls
Cx8- opaclues LhaL can progress Lo A8uS
Þerlpheral eoslnophllla
ulagnosls- 8AL, 188x
1reaLmenL- anuparasluc drugs- Lhlabendazole or
lvermecun
Med|canons (>140 reported)
Anubloucs*
uapLomycln*
ASA
Amlodarone
Cold SalLs
Cocalne- lnhaled
Peroln- lnhaled
L-LrypLophan
MeLhoLrexaLe
ÞhenyLoln
nlLrofuranLoln - rash,
pleural eñuslon
nSAlu*
SS8l
Sulfasalazlne
8leomycln
Mesalamlne
1reaLmenL -
d/c drug, +/- sLerolds

www.pneumoLox.com

Ç2- Wh|ch of the fo||ow|ng d|seases |s
character|zed by an absence of per|phera|
eos|noph|||a?
A. Chronlc eoslnophlllc pneumonla
8. Pypereoslnophlllc syndrome
C. AcuLe eoslnophlllc pneumonla
u. Loslnophlllc CranulomaLosls wlLh Þolyangllus
(Churg- SLrauss Syndrome)
Id|opath|c Acute Los|noph|||c Þneumon|a
Can be severe
?ounger, sllghL male predomlnance
usually healLhy
AssoclaLed wlLh Lhe recenL onseL of smoklng*, dusL,
envlronmenLal sumull, W1C
AcuLe onseL
Id|opath|c Acute Los|noph|||c Þneumon|a:
D|agnos|s
AcuLe febrlle lllness < 3 days ln durauon (cough, c/p,
myalglas)
Pypoxemlc resplraLory fallure
ulñuse alveolar or mlxed alveolar and lnLersuual
opaclues on chesL lmaglng
8AL eoslnophllla > 23° (can be near 30°)
Absence of parasluc, fungal lnfecuon, drugs, asLhma
8apld and compleLe response Lo corucosLerolds
8are Lo have perlpheral eoslnophllla (aL leasL early)*
Acute Los|noph|||c Þneumon|a
Cx8- paLchy opaclues, A8uS, small eñuslons ln
2/3rds
ÞaLhology- eoslnophlls ln alveoll, bronchlal walls and
+/- lnLersuuum, uAu
LlevaLed 8AL lL-3, vLCl, lL-18, and serum lgL
1reaLmenL- sLerolds- 2-8 weeks
usually, compleLe and rapld response
8elapse ls rare
Ç3- A S0 yo woman presents w|th 2 months of |ow grade
fevers, cough, a S |b. we|ght |oss and progress|ve SC8. She
has a h]o asthma. Labs are notab|e for 4S¼ eos|noph||s |n
b|ood. IgL |s 300 ng]m|. ÞI1s revea| obstrucnon and her
chest |mag|ng |s shown be|ow:
C3- 1he mosL llkely dlagnosls ls:
A. Loslnophlllc CranulomaLosls wlLh Þolyangllus
(Churg- SLrauss Syndrome)
8. Pypereoslnophlllc syndrome
C. Chronlc eoslnophlllc pneumonla
u. Allerglc bronchopulmonary asperglllosls
Chron|c Los|noph|||c Þneumon|a
Mlddle aged women
1/3 Lo 1/2 wlLh aLopy, asLhma
SubacuLe-chronlc presenLauon (wks-monLhs)- cough,
fevers, sweaLs, welghL loss, dyspnea, wheezlng
Þerlpheral blood eoslnophllla > 30° ln nearly 90°
8AL > 30-40° eoslnophllla
LlevaLed lgL
Þl1s- obsLrucuon
Chron|c Los|noph|||c Þneumon|a
8adlographs
– non-resolvlng pneumonla
– Þerlpheral, pleural based, dense, CCC opaclues
– ÞhoLographlc negauve of pulmonary edema < 30°
ÞaLhology
– Loslnophlllc lnñlLraLes ln alveolar spaces and lnLersuuum
– 8ronchlollus obllLerans
– Mlcroabscesses
– non-caseaung granulomas
Chron|c Los|noph|||c Þneumon|a
Loslnophll ls llkely a paLhogen
lL-3, lL-6, lL-10
LlevaLed lgL
1reaLmenL- sLerolds for 3-6 monLhs
lmprove over hours Lo days
8elapse ln 1/3-1/2
ALÞ vs CLÞ
AculLy AsLhma 8lood
Los
8AL
Los
Cx8 1reaLmenL
ALÞ acuLe,
severe
< 7 days
+/- absenL hlgh dlñuse, CCC,
pleural
eñuslons
sLerolds,
rare
relapse
CLÞ chronlc,
mllder,
weeks-
monLhs
30-60° mlld-
mod
hlgh perlpheral
consolldauon
sLerolds,
common
relapse
Id|opath|c nypereos|noph|||c Syndrome
?oung- mlddle aged males
8ange of severlLy
Muluorgan sysLems añecLed- lungs 40°, cardlac
unchecked lL-3
ulagnosls
– Loslnophllla > 1300/mm
3
for > 6 monLhs
– Lnd organ dysfuncuon
– no oLher cause of eoslnophllla
1reaLmenL- sLerolds (varlable response), lln-alpha,
chemoLherapy, hydroxyurea, lmaunlb
Mepollzumab (anu-lL3)
Los|noph|||c Granu|omatos|s w|th Þo|yang||ts
(LGÞA)- Churg-Strauss Syndrome
Allerglc granulomaLosls and angllus
8are- 2.7/mllllon/year
Ages 38-30, M>l
necrouzlng eoslnophlllc vascullus
SubacuLe
1hree Þhases
– AsLhmauc (Þrodromal 8-10 yrs)- allerglc rhlnlus, aLopy
– Loslnophlllc-perlpheral and ussue eoslnophllla- lungs, Cl, skln
– vasculluc- necrouzlng vascullus of small and medlum vessels,
exLravascular granulomas- consuLuuonal sympLoms
LGÞA-C||n|ca| I|nd|ngs
AsLhma- 99-100°
Þerlpheral nerve = 73° (mononeurlus muluplex)
Slnus dlsease = 70°
Skln = 30°. purpura, nodules, peLechlae
Lung- 38-38°- opaclues, eñuslons. uAP ls rare < 3°
Cl=30°
kldney = 23°. Aln, lSCn
PearL = 12°. CPl, CM. M and M
CnS = 10°
ConsuLuuonal
Am ! Med 2003. 113: 284
Medlclne 1999. 78: 26
LGÞA
D|agnos|s- the presence of 4]6 cr|ter|a
AsLhma*
Þerlpheral eoslnophllla > 10°
Mono or polyarLhropaLhy
MlgraLory pulmonary opaclues- nodules, CCC,
cavlLauon
Þaranasal slnus abnormallues
LxLravascular eoslnophlls on blopsy l.e. eoslnophlllc
vascullus
LGÞA
lmmune medlaLed
Þerlpheral eoslnophllla
8AL eoslnophllla
LlevaLed lgL
Þ-AnCA- MÞC-AnCA ln 2/3 and may correlaLe wlLh
vascullus
AnCA/MÞC negauve- correlaLes wlLh eoslnophlllc
lnñlLrauon -cardlac
ÞaLhology- lnLersuual eoslnophlllc ussue lnñlLrauon,
necrouzlng vascullus of small Lo medlum vessels,
granulomas
LGÞA
LeukoLrlene recepLor anLagonlsLs
– unmasklng LCÞA as sLerolds are decreased wlLh
L18A
– Causal
– CLher drugs may do Lhls
lnhaled CS
omallzumab
LGÞA- 1reatment
Þoor prognosls lf unLreaLed
SLerolds, azaLhloprlne, M1x
8elapses common
+/- CyLoLoxlc Lherapy- cyclophosphamlde
Second llne- lvlC, plasmapheresls, rlLuxlmab
use for severe and/or llfe LhreaLenlng organ
lnvolvemenL- hearL, CnS, mononeurlus, renal
Nonasthmanc Los|noph|||c 8ronch|ns
Cause of chronlc cough
no Cx8 ñndlngs, no varlable alrway obsLrucuon, no
alrway hyperresponslveness
Loslnophlls presenL ln Lhe spuLum or 8AL
8esponds Lo sLerolds
1reaLmenL lnhaled CS
Summary of key Þo|nts
Many dlsorders ln Lhls group of dlseases
know ALÞ vs CLÞ, A8ÞA, Loslnophlllc CranulomaLosls
wlLh Þolyangllus, Pypereoslnophlllc Syndrome
know whlch dlseases usually have perlpheral vs 8AL
eoslnophllla or boLh
MosL are corucosLerold responslve