What are we going to do about Emma

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What are we going to do about Emma?

• Dr Mark Rosenthal
• Royal Brompton Hospital
• London

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Born 4/10/90

• CF diagnosed age 4/12 (Feb 1991), because of
  cough and FTT from age 2/52.- had first ivs at
  that time.
• Wt 3rd centile, ht 25 to 50th
• ?F508/?F508
• RBH care from March 1991 onwards.

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March 1991 age 5 months
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Born 4/10/90

• Cough/wheeze was persisting symptom
• On nebulised pulmicort/ketotifen
• June 1991 well.
• Readmitted July 1991 for ivs Already on nebulised
  pulmicort/atrovent/ventolin

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Ages 14-20 months

• Dec1991 wt 50th centile , abdomen always pot
  bellied.
• June1992 Mother had chicken pox emma had
  acyclovir.
• Persistently pot bellied
• Taking up to 95 Creon 25000 per day to control
  stools other GIT tests all negative
• August 1992 1st isolation of Pseudomonas. Started
  on Gentamicin and Colomycin nebulisers

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The Torture of Emmas wheezing

• Symptoms of wheezing and coughing now taking
• centre stage - IgE 25 (lt49) Aug 1992
• First course of prednisolone May 1993
• 4th admission June 1993 IgE 47, Aspergillus Rast
  Pos, Precipitins Neg
• 5th admission Jan 1994 (age 3 y) Clinically
  hyperinflated. 1st presence of clubbing

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The Torture of Emmas wheezing

• 6th admission April 1994 Marked clubbing, IgE
  125, Aspergillus precipitins neg
• All cough, SOB and wheezing
• Began DNAse Sept 1994 very good clinical
  result

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Age 30 months
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The Torture of Emmas wheezing

• 3 further course of prednisolone plus inhaled
  pulmicort to 1600mcg/day
• Oct 1995 IgE 442 (from 84 in 1994)

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Height and Weight z scores
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Would You

• A) Think the decline in height z score is an
  inevitable consequence of CF
• B) Think that this is largely related to
  inhaled/oral steroid therapy
• C) Send her to GOS

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Height and Weight z scores
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The Torture of Emmas wheezing

• Dec 1995 (age 4) Referrred to endocrinologists
  for concerns re height steroid related no other
  hormonal reason
• Remains very wheezy and now pulmicort to
  3000mcg/day nebulised

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The Torture of Emmas wheezing

• April 1996 7th admission prolonged course of
  prednisolone for 6 months. IgE1055
• July 1996 Home ivs Ig E 500
• Dec1996 still on prednisolone 6mg/day Ig E 593.
• Aspergillus precipitins strongly positive.
  Started on long term azithromycin
• April 1997 still on Prednisolone 3mg alternate
  days
• Intermittant DIOS all investigations negative.

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Nov 1996 Age 6
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The Torture of Emmas wheezing

• October 1997 (Age 6) still cant be got off
  prednisolone/dexamethasone
• Bronchoscopy.

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What did the bronchoscopy show

• A) Marked inflammation and thick inspisated
  sputum
• B) Tracheobronchomalacia to account for her
  wheezing
• C) mild inflammation and trivial sputum

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The Torture of Emmas wheezing

• Bronchoscopy no sputum no inflammation no
  malacia
• Nov 1997 no real sputum and no growth for 1 year.
  Cushingoid, clubbed.
• Dec1997 stop pulmicort, start flixotide!
• Prednisone stopped July 1998 (28 months)
• Fastest runner in her class!
• Started on itraconazole

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The Torture of Emmas wheezing

• Admitted Nov 1998 ivs
• February 1999 (age 8) IgE 5648, Asp rast 101.
• Prednisolone restarted. ivs.
• Continuing Itraconazole (and azithromycin and
  DNAse Flixotide 1mg bd). Coughing up brown
  plugs
• Prednisolone continued for 6 months even needing
  1mg alternate days

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The Torture of Emmas wheezing

• August 1999 - very symptomatic Ig E 6500 FEV1
  69 (recent best is 80).

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The course of IgE
Prednisolone
Azithromycin
Itraconazole
Lobectomy
DNAse
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Aug 1999 age 8.8
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Aug 1999 age 9
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Would You (bearing in mind it is 1999).

• A) start a steroid sparing therapy
• B) start iv liposomal amphotericin
• C) send her to GOS

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The Torture of Emmas wheezing

• Started on ivs 6/52 liposomal amphotericin
• Fantastic response FEV1 122. IgE 3078.
• 6/52 later FEV1 56! Begin nebulised
  amphotericin/ 4/52 later FEV1 89

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The Torture of Emmas wheezing

• February 2000 (age 9) declining again. Liver
  function mildly deranged Hep ABC neg. CMV IgM
  ve. Steroids restarted.
• March 2000 still not right repeat iv liposomal
  amphotericin (liver function still abnormal
  therefore only 1mg/kg for 2 weeks)
• June 2000 still the same IgE 1349. Asp
  precipitins 3 lines/2 lines 3rd course of
  liposomal amphotericin no real benefit

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The Torture of Emmas wheezing

• July 2000. Restart dexamethasone (less fluid
  retention).
• Still pot bellied

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July 2000. Age 9.5
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Would You.

• A) start a steroid sparing agent
• B) perform a lobectomy
• C) send her to GOS

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The Torture of Emmas wheezing

• October 2000 right middle lobectomy.
  Histology..

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The Torture of Emmas wheezing

• October 2000 right middle lobectomy. Histology
  Numerous aspergillus hyphae no invasion
• VERY well!
• March 2001 stop steroids
• August 2001 return of symptoms. More ivs Ig E
  1300 (500 March 2001)
• Oct 2001 Ig E 2122

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May 2001 Age 10.5, 6/12 post lobectomy
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The Torture of Emmas wheezing

• Remember
• On DNAse since 1994
• On Azithromycin since 1996
• On Itraconazole since 1997
• On steroids on and off for 6 years
• 3 courses of iv liposomal amphotericin
• 3 bronchoscopies 1997, 2000, 2001
• Right middle lobectomy Oct 2000
• 37 course of iv antibiotics

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The Torture of Emmas wheezing

• Nov 2001 4th course of iv liposomal amphotericin
  plus methyl prednisolone 500mg/m2/ day for 3 days
• November 2001 began iv immunoglobulin therapy
  monthly for 6 months -No benefit
• April 2002 pulsed methyl prednisolone again
  severe joint pains

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The course of IgE
1st iv amphotericin
4th Ampho Ig rx
Prednisolone
Azithromycin
Itraconazole
Lobectomy
DNAse
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Dec 2002, age 12.1
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Would you.

• A) Start a steroid sparing agent
• B) Start a new antifungal agent voriconazole
• C) Do both A and B

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The Torture of Emmas wheezing

• October 2002 (11 years) trial of azathiaprine
  (IgE 2000) side effects severe headaches -
  stopped
• December 2002 Trial of voriconazole and
  methotrexate
• Feb 2003 admitted for DIOS requiring laparotomy
  and enterotomy
• May 2003 not too bad on MTX 12.5mg once a week
  and voriconazole.
• 2004 6 courses of ivs.
• Dec 2004 MTX stopped (NOT HELPING), still on
  voriconazole (and Azithromycin 8 years)
• Jan - May 2005 2 more courses of ivs

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The course of IgE
1st iv amphotericin
MTX voriconzole
4th Ampho Ig rx
Prednisolone
Azithromycin
Itraconazole
Lobectomy
MTX stopped
DNAse
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Formal Lung Function
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Height and Weight z scores
To Endocrinologist
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March 2005. Aged 14.5
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As we are in the same place as we were in 1996,
have we.

• A) Fallen into the trap of a genuinely ill child
  plus over-anxious family and over-treated
• B) Saved her from dying very prematurely by
  ultra-aggressive therapy
• C) Failed to send her to GOS

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You know.

• Im really not sure.
• THE END

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Age 2
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Oct 1995 age 5
October 1995. Age 5
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Age 5.5 April 1996
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July 1997. Age 6.5
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Age 8.3. Feb 99
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BRONCHIOLE WITH INFLAMMATION AND ASPERGILLUS
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