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SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT
CARE
SSC/SSCC-SSP
Congress
17. June 2016
Dr. med. Reta Fischer
PD Dr. Med. Alain Sauty
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
Why these recommendations ?
SWISS RECOMMENDATIONS
FOR ADULT CF CARE
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
•
Almost 50% of CF patients are adult
•
Consensus/guidelines provided by the ECFS, CF UK Trust
and other « authorities » often based on expert opinion and
often differ
•
Most centers follow their own proptocols
•
Need to share our experience between centers and to try to
harmonize our procedures
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
•
An example…
•
Should we try to eradicate M. abcessus when found 2 or 3
times in a CF patient ?
o
M. abcessus may be associated with very poor outcome in CF but
treatment is long, burdensome and may be unnecessary
o
The ATS/ERS recommend to treat M. abcessus in CF only if a
NTM disease is highly suspected
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
•
An example…
•
Should we try to eradicate M. abcessus when found 2 or 3
times in a CF patient ?
o
The Royal Brompton Hospital adult CF clinic (biggest in Europe)
presently try to eradicate M. abcessus…
o
The Toronto adult CF clinic (biggest in North America) currently
follows strictly the ATS/ERS recommendations …
o
What is our position in CH ?
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
•
Were initiated by Dr. med. Angela Koutsokera and
Dr. med. Alain Sauty to provide useful and concise
recommendations to caregivers involved in adult CF
•
All responsables of adult CF centers in CH were
contacted to participate to the elaboration of these
recommendations
•
These recommendations cover all subjects
concerning adult CF patients prior lung/liver
transplantation
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
•
An advisory board has been created which reviews
all the recommendations
•
A first release will be available by the end of 2016 or
beginning 2017 as an App for tablet and by internet.
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
Advisory board
PD Dr Christian BENDEN (University Hospital, Zürich)
Pr Jean-Marc FELLRATH (Hôpital Neuchatelois Pourtales,
Neuchâtel)
Dr Reta FISCHER (Lindenhof, Bern)
Pr Thomas GEISER (Inselspital, Bern)
Dr Markus HOFER (Hospital of Winterthur, Winterthur)
Dr Angela KOUTSOKERA (EHC/CHUV, Lausanne)
Pr Laurent NICOD (CHUV, Lausanne)
Dr Jérôme PLOJOUX (HUG, Genève)
Dr Rebekka KLEINER (Hospital of St. Gallen, St. Gallen)
PD Dr Alain SAUTY (EHC/CHUV, Lausanne)
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
Contributors (almost 50 articles)
PD Dr Christian BENDEN (University Hospital, Zürich)
Dr Jesica MAZZA-STALDER (CHUV, Lausanne)
Pr Laurent NICOD (CHUV, Lausanne)
Dr Jérôme PLOJOUX (HUG, Genève)
Dr Markus HOFER (Hôpital of Winterthur)
Dr Angela KOUTSOKERA (EHC/CHUV, Lausanne)
PD Dr Alain SAUTY (EHC/CHUV, Lausanne)
Pr Jean-Marc FELLRATH (H. Pourtales, Neuchâtel)
Dr Daniel WIRTHNER (CPMA, Lausanne)
Dr Marc WISARD (CPMA, Lausanne)
Dr Maura PRELLA (CHUV, Lausanne)
Pr Thierry ROCHAT (HUG, Genève)
Pr John-David AUBERT (CHUV, Lausanne)
Pr Christian VANDELDEN (HUG, Genève)
Pr Claudia MAZZOCATO (CHUV, Lausanne)
PD Alice PANCHAUD (CHUV, Lausanne)
Dr Ermindo Di Paolo (CHUV, Lausanne)
PD Dr Olivier LAMY (CHUV, Lausanne)
Pr Christoph SCHMID (University Hospital, Zürich)
Dr Michael MORRIS (SynLab, Switzerland)
Marta KERSTAN-HUBER (DePuy Synthes, Zürich)
Peter SUTER (University Hospital, Basel)
Dr Christian MURER (University Hospital, Zürich)
Urs BÜRGI (University Hospital, Zürich)
PD Dr Sarosh IRANI (Hospital of Aarau)
Cédric DUNANT(CHUV, Lausanne)
Pr Jean-Louis FROSSARD (HUG, Genève)
Dr Amineh TROENDLE (Lindenhof, Bern)
Dr TINI (Hospital Aarau)
PD Dr Roberto BULLANI (EHC, Morges)
Deborah HERSCH (CHUV, Lausanne)
PD Dr Valérie Mc LIN(HUG, Genève)
PD Dr Claudia MAZZOCATO (CHUV, Lausanne)
Aurélie ARTIBANI (CHUV, Lausanne)
PD Dr Pauline COTI BERTRAND (CHUV, Lausanne)
Dr Estelle CLOTTU (CHUV, Lausanne)
PD Dr Lars C. HUBER (University Hospital, Zürich)
Dr Rebekka KLEINER (Hospital of St-Gallen)
Pr Nicolas REGAMEY (Children’s Hospital, Lucerne)
Marie Hofer (EHC/CHUV, Lausanne)
Pr Christian VAN DELDEN (HUG, Genève)
PD Dr Oriol MANUEL(CHUV, Lausanne)
Pr Nicolas MÜLLER(University Hospital, Zürich)
Pr Nicolas REGAMEY(Children’s Hospital, Lucerne)
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
Sponsors
Mylan
Vifor
CFCH
Ligue Pulmonaire Vaudoise
Fondation Respirer
Case 1
as example using the
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
T.G. female 36 years old
• Referred for a second opinion.
• She complains of increasing productive cough
and shortness of breath. She does have
purulent sputum with occasional hemoptysis.
• She describes troubles in gaining weight.
• She denies fever, chills or sweats.
• She is a nonsmoker and is married. Since 4
years she is trying to get pregnant.
T.G. female 36 years old
• She is known for several pneumonias in childhood
and was treated for a allergic Asthma bronchiale.
• In 2008 she was treated with systemic steroids for
9 months with improvement of shortness of breath.
• Actually she just uses Bricanyl® when needed.
T.G. female 36 years old
On physical examination
• Afebrile with stable vital signs
• BMI 18.4 kg/m2
• Oxygen saturation 98% breathing room air
• Bilateral scattered crackles on lung
examination
• No lymphadenopathy and no clubbing.
T.G. female 36 years old
Lung function
•
Severe Obstruction,
FEV1 49% pred. (1.49 l)
•
Air Trapping
•
DLCO 78% pred.
•
FeNO 14 ppb
T.G. female 36 years old
Her laboratory examination show :
• Leucocytes 7.9 Giga/l
• Eosinophils 0.75 Giga/l (9.5%)
• BSR 12 mm/h, CRP 8.3 mg/l
• Total IgE 4960 kU/l
T.G. female 36 years old
Sputum:
• Staphylococcus aureus ++
• Aspergillus fumigatus +
• Candida albicans +
More laboratory examinations show:
• IgE for Aspergillus fumigatus 36.9 kU/l (Rast 4)
• Rekombinant Allergens rf1, rf3, rf4 and rf6 strongly
positiv
• Normal IgG, IgM, IgA, HIV negativ
T.G. female 36 years old
Diagnosis:
• ABPA
• Clinical suspicion of Cystic Fibrosis or CFTR-RD
What are the next steps?
Clinical suspicion of CF or CFTR-RD
in an adult patient
1st level CFTR DNA test and sweat test
0 CF-causing variant
1 CF-causing variant
2 CF-causing variants in trans
Sweat test (repeat if abnormal)
Proceed to gene sequencing
independent of sweat test results
Sweat test
<30mmol/l 30-60mmol/l
>60mmol/l
Assess for causes of false
positive sweat test (Table
2)
No
Yes
<30mmol/l
30-60mmol/l >60mmol/l
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
Gene sequencing*
Gene sequencing*
0 CF-causing
variant
1 CF-causing variant
1 CF-causing variant and
1 CFTR-RD variant in trans
2 CF-causing variants in trans
Sweat test (repeat if abnormal)
Sweat test (repeat if abnormal)
Sweat test
<30mmol/l 30-60mmol/l >60mmol/l <30mmol/l 30-60mmol/l >60mmol/l <30mmol/l
30>60mmol/l
60mmol/l
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
CF Unlikely
Inconclusive
CFTR-RD
CF
Consider alternative
diagnoses, organize
appropriate investigations
Consider consultation in
an adult CF center
Consultation in
an adult CF center
Consultation in
an adult CF center
T.G. female 36 years old
CFTR Gen Test:
•
•
F508del
CF-causing variant
R117H – T7
CFTR-RD variant
Sweat Test:
•
Chlorid 38 mmol/l
Clinical suspicion of CF or CFTR-RD
in an adult patient
1st level CFTR DNA test and sweat test
0 CF-causing variant
1 CF-causing variant
2 CF-causing variants in trans
Sweat test (repeat if abnormal)
Proceed to gene sequencing
independent of sweat test results
Sweat test
<30mmol/l 30-60mmol/l
>60mmol/l
Assess for causes of false
positive sweat test (Table
2)
No
Yes
<30mmol/l
30-60mmol/l >60mmol/l
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
Gene sequencing*
Gene sequencing*
0 CF-causing
variant
1 CF-causing variant
1 CF-causing variant and
1 CFTR-RD variant in trans
2 CF-causing variants in trans
Sweat test (repeat if abnormal)
Sweat test (repeat if abnormal)
Sweat test
<30mmol/l 30-60mmol/l >60mmol/l <30mmol/l 30-60mmol/l >60mmol/l <30mmol/l
30>60mmol/l
60mmol/l
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
CF Unlikely
Inconclusive
CFTR-RD
CF
Consider alternative
diagnoses, organize
appropriate investigations
Consider consultation in
an adult CF center
Consultation in
an adult CF center
Consultation in
an adult CF center
Diagnostic terminology
Established CF diagnosis:
1) clinical features of CF iin at least one organ and 2) CFTR
dysfunction demonstrated through one of the three specific
diagnostic tests (i.e. the sweat chloride test, the CFTR gene
analysis or CFTR bioassays).
CFTR-RD:
mainly single organ clinical entities that do not fulfil the
diagnostic criteria of CF; they are characterized by clinical
findings of CFTR dysfunction and none or one CF causing
variant. The best-recognized CFTR-RD are:
•
•
•
congenital bilateral absence of the vas deferens
(CBAVD)
acute recurrent or chronic pancreatitis
diffuse bronchiectasis
3 months later (Flutter®, Fluimucil®, Seretide®)
• Lung function:
•
FEV1 71% pred. (2.12 l)
- +630 ml
- 49
71% pred.
• Sputum:
•
Pseudomonas aeruginosa
+
•
Staphylococcus aureus ++
• Pregnant (8 weeks)
T.G. female 36 years old
Pseudomonas Eradication Therapy ...
... in Pregnancy?
Panchaud A. et al. Respiration. 2016;91(4):333-48
Case 2
as example using the
SWISS RECOMMENDATIONS
FOR ADULT CF PATIENT CARE
O.T. female 20 years old
• F508del/F508del
• Lives between Prague and Switzerland
• Pancreatic insufficiency and CF-related
diabetes
• Bronchiectasis colonized by St. aureus and
B. cepacia contaminans since at least 2011
• Intermittent infection by Ps. aeruginosa
• Embolisation for hemoptysis in 2013
• ABPA in 2005 with recurrence in 2014
O.T. female 20 years old
• Typisation du B. cepacia (Prague) : ”contaminans”
O.T. female 20 years old
Table 1: B. cepacia complex species (adapted from1)
Species
Comments
B. cepacia
Infections in CF and non-CF patients. Associated to “cepacia syndrome”
B. multivorans
Infections in CF and non-CF patients. Associated to “cepacia syndrome”
B. cenocepacia
Infections in CF and non-CF patients. Associated to “cepacia syndrome”
B. stabiliz
Infections in CF and non-CF patients
B. vietnamiensis
Infections in CF and non-CF patients
B. dolosa
Infections in CF only
B. ambifaria
Infections in CF and non-CF patients
B. anthina
Infections in CF and non-CF patients
B. pyrrocinia
Infections in CF only
B. ubonensis
Infections in non-CF patients only
B. latens
Infections in CF only
B. diffusa
Infections in CF and non-CF patients
B. arboris
Infections in CF and non-CF patients
B. seminalis
Infections in CF and non-CF patients
B. metallica
Infections in CF only
B. contaminans
Infections in CF only
B. lata
Infections in CF and non-CF patients
CF patients with B. cepacia complex may
present with :
• Colonization without change in pulmonary
status.
• Infection with accelerated pulmonary
decline.
• Acute deterioration with life threatening
pneumonia and bacteriemia (“cepacia
syndrome”).
O.T. female 20 years old
O.T. female 20 years old
Table 1: B. cepacia complex species (adapted from1)
Species
Comments
B. cepacia
Infections in CF and non-CF patients. Associated to “cepacia syndrome”
B. multivorans
Infections in CF and non-CF patients. Associated to “cepacia syndrome”
B. cenocepacia
Infections in CF and non-CF patients. Associated to “cepacia syndrome”
B. stabiliz
Infections in CF and non-CF patients
B. vietnamiensis
Infections in CF and non-CF patients
B. dolosa
Infections in CF only
B. ambifaria
Infections in CF and non-CF patients
B. anthina
Infections in CF and non-CF patients
B. pyrrocinia
Infections in CF only
B. ubonensis
Infections in non-CF patients only
B. latens
Infections in CF only
B. diffusa
Infections in CF and non-CF patients
B. arboris
Infections in CF and non-CF patients
B. seminalis
Infections in CF and non-CF patients
B. metallica
Infections in CF only
B. contaminans
Infections in CF only
B. lata
Infections in CF and non-CF patients
O.T. female 20 years old
• July 4, 2015, becomes rapidly dyspneic with fever up
to 38°5C.
• Hypoxemic despite O2, CRP 151 mg/l, leuco 11.8 G/l
• Hemoculture July 4 : St. aureus, B. cepacia
contaminans
Rx thorax 4.7
CT thorax 8.7.15
CT thorax 26.09.14
CT thorax 8.7.15
CT thorax 26.09.14
CT thorax 8.7.15
CT thorax 26.09.14
Cepacia syndrome
B. cenocepacia infection, and more rarely B. cepacia and B.
multivorans infection, can cause life threatening pneumonia and
bacteriemia, called ‘cepacia syndrome’.
o Cepacia syndrome may occur early or many years after the
organism is first identified.
o Patients usually present with fever, leukocytosis, increased Creactive protein, patchy infiltrates or cavitary lesions on the
imaging studies (consolidations and abscesses).
o Growth of B.cepacia species in sputum and blood cultures may
take several days. A high clinical suspicion should lead to early
and aggressive treatment, even before microbiological diagnosis
is obtained knowing the high mortality rate of cepacia syndrome.
“Treatment of Cepacia syndrome“
Table 4: Treatment protocols used for Cepacia syndrome (adapted from9-12 )
Protocol based on
Regimen
Adult patient,
Meropenem + tobramycin IV + TMP/SMX IV + chloramphenicol
non-transplanted12
+ prednisolone (30-40 mg) + cyclosporine 50 mg IV 1x/day for 5 days then
50 mg orally 1x/day
At discharge (after 35 days): inhaled meropenem + cyclosporin
Adult patient,
Meropenem IV + tobramycin IV + TMP/SMX IV + temocillin + inhaled
5 years after
meropenem + inhaled tobramycin
liver/pancreas
At discharge (after 50 days): inhaled meropenem and tobramycin
transplantation10
Pediatric patients (n=2)9 Case 1: ceftazidime + meropenem + ciprofloxacine + chloramphenicol +
TMP/SMX + methylprednisolone
Case 2: ceftazidime + tobramycine + TMP/SMX + inhaled tobramycine +
rhDNase
O.T. female 20 years old
•
•
•
•
Meropenem (4h iv perfusion 3x/day) + cefta iv +
tobramycine iv + TMP/SMX orally
Cefta inh (1 g 2x/j)
Prednisone 10 mg/j
9/7, because of unfavorable evolution, tigecycline iv
and azithromycine orally were added
CT thorax 15.8
CT thorax 16.7
CT thorax 15.8
CT thorax 16.7
CT thorax 15.8
CT thorax 16.7
O.T. female 20 years old
•
•
Total AB treatment : 6 weeks
At discharge, tobra inh 1 month/2 and meropenem
inh (500 mg) 2x/d 1 mois/2 + azithromycine 500 mg
3x/sem.
O.T. female 20 years old
Cepacia
syndrome
“Treatment of Cepacia syndrome“
Table 4: Treatment protocols used for Cepacia syndrome (adapted from9-12 )
Protocol based on
Regimen
Adult patient,
Meropenem + tobramycin IV + TMP/SMX IV + chloramphenicol
non-transplanted12
+ prednisolone (30-40 mg) + cyclosporine 50 mg IV 1x/day for 5 days then
50 mg orally 1x/day
At discharge (after 35 days): inhaled meropenem + cyclosporin
Adult patient,
Meropenem IV + tobramycin IV + TMP/SMX IV + temocillin + inhaled
5 years after
meropenem + inhaled tobramycin
liver/pancreas
At discharge (after 50 days): inhaled meropenem and tobramycin
transplantation10
Pediatric patients (n=2)9 Case 1: ceftazidime + meropenem + ciprofloxacine + chloramphenicol +
TMP/SMX + methylprednisolone
Case 2: ceftazidime + tobramycine + TMP/SMX + inhaled tobramycine +
rhDNase
Our experience
Meropenem + ceftazidime IV and inhaled + tobramycin IV + TMP/SMX oral
+ tigecycline + azithromycine + prednisone (10-20 mg/day) for 6 weeks