Imaging  of  thoracic  aspergillosis  

Prof.  G  FERRETTI  CHU  GRENOBLE  

 

HANOI,  NOV  2015  

Aspergillus  diseases    

•  Aspergillus  species  (A  fumigatus)  •  saprophyAc,  aerobic  fungus  that  develops  on  dead  or  decaying  organic  maNer  and  produces  airborne  spores  that  can  be  inhaled  by  man  

•  Four  presentaAons  according  to  clinical  presentaAon  and  state  of  immunity      ü Hypersensi0vity  reac0on  (ABPA)    ü Aspergilloma  ü Semi-­‐invasive  (chronic  necro0zing)  aspergillosis  ü Invasive  aspergillosis  Angioinvasive  vs.  Airway-­‐invasive  

Godet  C  Respira0on  2014;88:162-­‐174  

   1-­‐  Allergic  bronchopulmonary  

aspergillosis  (ABPA)    Secondary  to  anAgens  released  by  Aspergillus  fumigatus  that  colonizes  the  tracheobronchial  tree  Pathogenesis  :  Aspergillus-­‐specific  IgE-­‐mediated  Type  I  hypersensiAvity  reacAon  /  specific  IgG-­‐mediated  Type  III  hypersensiAvity  reacAons      Progressive  disease  with    

–  recurrent  exacerbaAons    –  bronchiectaAc  changes    –  end-­‐stage  fibrosis    

•  Under  diagnosed  disease  •  Early  diagnosis  and  treatment  prevents  its  progression  and  alleviate  its  

clinical  manifesta0ons.    •  High  resolu0on  CT  of  the  chest  has  emerged  as  a  promising  inves0ga0on  

for  its  diagnosis.  DW  Denning,  Clin  Transl  Allergy.  2014  

Clinical  presentaAon  

•  Common  contribuAng  factor:  –  asthma  (the  most  frequent)  –  cysAc  fibrosis    –  other  underlying  bronchiectaAc  diseases    

•  ABPA  occurs  in  0.25%-­‐11%  of  paAents  with  asthma  Novey  JS.  Epidemiology  of  allergic  bronchopulmonary  aspergillosis.  Immunol  Allergy  Clin  North  Am.  

1998;18:641-­‐53.    

 

•  Poorly  controlled  asthma,  hemoptysis,  weight  loss  and  fever.  

  Morgan  J,  Med  Mycol,  2005  

ABPA  Central  bronchiectasis  with  predilecAon  for  

upper  and  middle  lobes  (78%)  

ABPA  with  recent  exacerba>on    

70  yo  man  ABPA  recent  exacerbaAon  Tree  in  buds    Dense  mucocele  which  is  specific  for  ABPA    

56 yo man, COPD, asthma, acute exacerbation

10  

Imaging  presentaAon  •  Diagnosis  of  APBA  is  frequently  missed  on  chest  X  ray  which  is  normal  in  almost  50%  of  the  cases    

Agarwal  R,  et  al.  Pictorial  essay:  Allergic  bronchopulmonary  aspergillosis.  Indian  J  Radiol  Imaging.  2011  Oct-­‐Dec;  21(4):  242–52.    

•  HRCT  May  be  normal  (23%)  •  Abnormal  HRCT  scan  

–  Central  bronchiectasis  with  predilecAon  for  upper  and  middle  lobes  (78%)  

–  Centrilobular  nodules  with  or  without  linear  opaciAes  (tree  in  bud  paNern):  86%  

– Mucoceles:  59%  –  High-­‐aSenua0on  mucus:  36%  of  cases  calcium  salts  and  metals  (iron  and  manganese)  or  desiccated  mucus    

2-­‐Aspergilloma  or  Saprophy0c  aspergillosis    

•  Aspergillus  infecAon  without  Assue  invasion  •  leads  to  conglomeraAon  of  fungal  hyphae  admixed  with  mucus  and  cellular  debris  within  a  preexistent  pulmonary  cavity  or  ectaAc  bronchus  

•  ComplicaAon  of  Tuberculosis  /  sarcoidosis  IV  /  bronchectasis  /  pneumatocele    

•  The  most  common  symptom  is  hemoptysis    •  The  source  of  bleeding:  bronchial  arteries  or  anastomoAc  communicaAons  between  pulmonary  and  bronchial  arteries  associated  with  the  aspergilloma.  

History  of  tuberculosis  

HIV+  paAent  History  of  aspergilloma  since  2005  

Early  aspergilloma  Pleural  thickening  

Imaging  Aspergilloma  

•  CXR  /  CT  – ovoid  or  round  opacity  located  within  a  lung  cavity    –  localized  pleural  thickening  best  appreciated  on  CT  – crescent  of  air  around  the  mycetoma:    separaAon  of  the  fungal  mass  from  its  surrounding  cavity  wall    

– posi0onal  changes  of  the  intra-­‐cavitary  mass  during  imaging  may  indicate  its  mobility  within  the  cavity.    

Stage IV sarcoidosis Occurrence of hemoptysis

Aspergilloma Bronchial artery

embolisation

3-­‐  Chronic  Pulmonary  Aspergillosis:  significa0on    

Due  to  existence  of  overlapping  clinico-­‐radiologic  phenotypes  that  may  follow  variable  courses,  the  term  ‘CPA’  may  be  used  to  encompass:    

ü simple  aspergilloma    ü CCPA  (chronic  cavitary  pulmonary  aspergillosis)    ü CFPA  (chronic  fibrosing  pulmonary  Aspergillosis)    ü CNPA  (chronic  necroAsing  pulmonary  aspergillosis)  being  classified  as  a  sub-­‐acute  form  of  IPA  

Affects  individuals  with  non-­‐systemic  or  mildly  systemic  immunodepression  or  altered  pulmonary  integrity  due  to  underlying  disease.      All  paAents  share  the  clinical  presentaAon:  weight  loss,  fa0gue  and  chronic  cough,  +/-­‐  chest  pain  and  hemoptysis    lung  parenchyma  alteraAons  results  mostly  from  the  lung  immune/inflammatory  response  against  Aspergillus  spp.  rather  than  from  direct  invasion  by  the  fungi    CPA  generally  requires  long-­‐term  an0fungal  treatment  .  High  morbidity  and  mortality.  

Chronic  pulmonary  aspergillosis  (CPA)    

Franquet  T  Radiographics  2001;  21:  825–837.  

35  yo  man  sere  pneumonia  in  2014.  absence  of  cavity  but  progressive  destrucAon  of  the  LUL  

Dg:  CPA    

CPA  in  a  50-­‐year-­‐old  paAent.  A  large  cavity  filled  with  a  typical  fungus  ball  surrounded  by  an  air  crescent  is  seen  in  a  partly  collapsed  lel  upper  lobe.    The  pleura  are  thickened  and  the  remaining  lel  lung  shows  distorAon  features.  

Role  of  CT  Scan  Imaging  in  CPA  Diagnosis  •  CT  provides  useful  informaAon  regarding    1/  the  characterisAcs,  2/  distribuAon  

3/extent  of  features  Kim  SY  AJR  2000;  174:  795–798.  

Franquet  T  Radiographics  2001;  21:  825–837.  •  CT  findings  of  CPA    are  non-­‐specific  and  can  be  encountered  in  TB,  

ac0nomyosis  and  lung  carcinoma.  

•  In  a  proper  clinical  seZng,  the  diagnosis  of  CPA  can  be  suggested  on  CT  –  unilateral  or  bilateral  areas  of  consolida0on,  frequently  with  one  or  several  cavita0ons  containing  fungus  balls  in    about  50%  of  cases  (most  frequent)  

–  thickening  of  the  walls  of  cavitaAon  and  pleura  –  areas  of  consolidaAon  or  of  ground  glass  aNenuaAon  in  the  surroundings.  

–  pulmonary  nodules  of  varying  sizes  may  be  present  (tree-­‐in-­‐bud  sign)  

–  LocalizaAon:  upper  lobes,  that    frequently  appears  collapsed  

Soubani  AO,  Chest  2002;  121:  1988–1999.  

Chronic  pulmonary  consolida0on  in  the  right  upper  lobe  Pa0ents  with  COPD,  diabetes    and  alcoholism  Diagnos0c:  trans  thoracic  biopsy  and  then  surgery  

CPA  

75  yo  woman    chronic  lung  parenchyma  consolida0on  with  cavita0ons  Severe  altera0on  of  general  state  Diabetes  mellitus      

Mucormycosis

15  10  2012  

28  02  2012  Lung adenocarcinoma  

Differen0al  diagnosis    

•  Differen0al  diagnosis    – TB,  non-­‐TB  mycobacterial  infecAon,  histoplasmosis  coccidiomycosis…  

–  lung  cancer,  rheumatoid  arthriAs,  sarcoidosis  •  Before  considering  the  treatment  of  probable  CPA  and  in  the  absence  of  absolute  diagnos0c  criteria  for  CPA,  it  seems  necessary  to  eliminate  the  diagnosis  of  lung  cancer  or  other  associated  infecAons  by  any  means  (repeated  biology,  bronchoscopy,  CT)  

Denning  DW  Clin  Infect  Dis  2003;  37(suppl  3):  S265–S280.  

Role  of  bronchial  embolisa0on  

•  Hemoptysis  is  the  cause  of  death  in  up  to  26%  of  paAents  with  condiAons  including  aspergilloma  and  complex  aspergilloma/CPA  

•  BAE  achieves  immediate  control  of  hemoptysis  in  91.6%  of  aspergilloma  paAents  within  24  h  

•  Any  paAent  with  even  minimal  hemoptysis  should  be  promptly  invesAgated  by  CTA  +  BAE  

Stevens  DA  Clin  Infect  Dis  2000;  30:  696–709.  

4-­‐  Invasive  aspergillosis  •  affects  mainly  the  lungs  •  is  an  important  cause  of  mortality  and  morbidity  in  paAents  with  –  hematologic  malignancies  (prolonged  neutropenia)  (<25%)  –  recipients  of  allogeneic  hematopoieAc  stem  cell  transplants  (<10%)  –  prolonged  use  of  corAcosteroids  and/or  T-­‐cell  immunosuppressants  

•  The  diagnosis  is  difficult  to  make:  –  Assue  specimen  (rarely  obtained)  –  associa0on  of  a  host  factor,  lung  CT  findings,  and  microbiologic  findings  either  direct  tests  (such  as  direct  microscopy  or  culture)  or  indirect  tests  (such  as  galactomannan  an0gen  [GM]  or  β-­‐D  glucan)  

CT  scanning:  a  cornerstone  •  nodule  with  a  halo  sign:    highly  suggesAve  of  IPA  in  

neutropenic  pa0ents    Caillot  D  et  al.  J  Clin  Oncol.  2001;19(1):253-­‐  259.  

•  liNle  is  known  about  CT  scan  features  in  non-­‐neutropenic  pa0ents:  up  to  40%  of  paAents  with  IPA  do  not  present  with  a  nodule  with  a  halo  sign.  

Greene  R.  Med  Mycol.  2005;43(supl  1):  S147-­‐S154.  

•  2  different  pa7erns  of  IPA  

–  angioinvasive  pulmonary  aspergillosis  is  characterized  by  vascular  invasion  by  Aspergillus  and  a  nodule  with  a  halo  sign  

–  airway-­‐invasive  aspergillosis  is  characterized  by  the  destrucAon  of  the  bronchiolar  wall  by  Aspergillus  and  centrilobular  micronodules  and  tree-­‐in-­‐bud  opaciAes  (14%  to  34%  of  cases  of  IPA)  

Franquet  T  et  al.  J  Comput  Assist  Tomogr.  2004;28(1):10-­‐16.  

•  Angioinvasive.  Histology  of  a  nodule  with  a  halo  sign  demonstrates  occlusion  of  arteries  by  plugs  of  hyphae  and  the  subsequent  development  of  infected  pulmonary  infarcts:  poor  mycologic  diagnos0c  yield  

 angioinvasive          bronchoinvasive  

•  Bronchoinvasive.  Histologic  examinaAon  of  airway-­‐invasive  aspergillosis  shows  colonies  of  Aspergillus  invading  through  bronchiolar  walls  together  with  peribronchiolar  inflammaAon:  high  performance  of  mycologic  examina0on  

Franquet  T  et  al.  J  Comput  Assist  Tomogr.  2004;28(1):10-­‐16.  

halo sign strongly suggests angioinvasive aspergillosis when it occurs in a patient with neutropenia who is receiving cytotoxic therapy and broad-spectrum antibiotic, but non specific (candidiasis, CMV, Kaposi sarcoma)

55  yo  man  –  acute  leukemia  under  chemotherapy.    Chest  pain  and  liNle  fever    

Follow-up CT scan in the same patient with angioinvasive aspergillosis

à J15

à J30

Clinical  InfecAous  Diseases  2011;52(9):1144–1155  

16  10  2013  

22  10  2013  

Bronchoinvasive  Aspergillosis  •  3  types    

Ø  obstrucAve,    Ø  ulceraAve  Ø  Pseudomembranous  

•  co-­‐exisAng  presentaAon++  

•  Neutropenia  and  systemic  immunosuppression  are  major  risk  factors    

•  increasing  frequency  among  lung  transplant  recipients  and  paAents  with  chronic  auto  immundiseases,  acquired  immune  deficiency  syndrome  (AIDS)  and  malignancy  

•  62  yo  man  •  Recent  faAgue  weigh  loss  anorexia    •  Fever    •  Cough  •  acute  respiratory  distress…  ICU  

Aspergillus  tracheobronchiAs  

•  Symptoms  may  be  non-­‐specific  including  cough  in  the  majority,  dyspnoea,  blood-­‐stained  sputum,  night  sweats,  fever  and  wheeze  which  may  be  asymmetric.  

•  Radiographic  findings  include  endo-­‐bronchial  sol  Assue  thickening,  obstrucAon  and  tracheobronchial  stenosis  leading  to  segmental  or  subsegmental  lobar  collapse  

•  Bronchoscopic  examinaAon  and  mucosal  biopsy  is  essenAal  for  accurate  diagnosis.  Macroscopic  findings  include  luminal  obstrucAon,  mucosal  ulceraAon  and  exudaAve  pseudomembranes  adherent  to  the  underlying  mucosa  while  microscopic  demonstraAon  of  fungal  elements  is  both  sensiAve  and  specific  for  Aspergillus  tracheobronchiAs  and  allows  a  confident  diagnosis  to  be  made  

Conclusion  •  Imaging  plays  an  important  role  in  aspergillus  related  diseases  

•  Always  remember  that  imaging  is  dependent  on  clinical  presenta0on  and  state  of  immunity      o Hypersensi0vity  reac0on  (ABPA)  o Aspergilloma  o Semi-­‐invasive  (chronic  necro0zing)  aspergillosis  o Airway-­‐invasive  aspergillosis  o Angioinvasive  aspergillosis