SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE · SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE...
Transcript of SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE · SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE...
Dr. med. Reta Fischer
PD Dr. Med. Alain Sauty
SWISS RECOMMENDATIONSFOR ADULT CF PATIENT
CARE
SSC/SSCC-SSP Congress
17. June 2016
Why these recommendations ?
SWISS RECOMMENDATIONSFOR ADULT CF PATIENT CARE
SWISS RECOMMENDATIONSFOR ADULT CF 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 RECOMMENDATIONSFOR 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 RECOMMENDATIONSFOR 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 RECOMMENDATIONSFOR 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 RECOMMENDATIONSFOR 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 RECOMMENDATIONSFOR 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 RECOMMENDATIONSFOR ADULT CF PATIENT CARE
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)
Contributors (almost 50 articles)
SWISS RECOMMENDATIONSFOR ADULT CF PATIENT CARE
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)
Sponsors
Mylan
Vifor
CFCH
Ligue Pulmonaire Vaudoise
Fondation Respirer
SWISS RECOMMENDATIONSFOR ADULT CF PATIENT CARE
Case 1
as example using the
SWISS RECOMMENDATIONSFOR ADULT CF PATIENT CARE
• 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 childhoodand was treated for a allergic Asthma bronchiale.
• In 2008 she was treated with systemic steroids for9 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?
T.G. female 36 years old
Clinical suspicion of CF or CFTR-RD
in an adult patient
1st level CFTR DNA test and sweat test
1 CF-causing variant 2 CF-causing variants in trans
Sweat test
Gene sequencing*
1 CF-causing variant 1 CF-causing variant and
1 CFTR-RD variant in trans
CF Unlikely CFTR-RD CFInconclusive
Assess for causes of false
positive sweat test (Table
2)
0 CF-causing variant
Sweat test (repeat if abnormal)
<30mmol/l 30-60mmol/l >60mmol/l <30mmol/l 30-60mmol/l >60mmol/l
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
Yes No
Sweat test (repeat if abnormal)
<30mmol/l 30-60mmol/l >60mmol/l
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
2 CF-causing variants in trans
Sweat test
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
Sweat test (repeat if abnormal)
<30mmol/l 30-60mmol/l >60mmol/l <30mmol/l 30-
60mmol/l
>60mmol/l
Proceed to gene sequencing
independent of sweat test results
Gene sequencing*
0 CF-causing
variant
CFTR Gen Test:
• F508del CF-causing variant
• R117H – T7 CFTR-RD variant
Sweat Test:
• Chlorid 38 mmol/l
T.G. female 36 years old
Clinical suspicion of CF or CFTR-RD
in an adult patient
1st level CFTR DNA test and sweat test
1 CF-causing variant 2 CF-causing variants in trans
Sweat test
Gene sequencing*
1 CF-causing variant 1 CF-causing variant and
1 CFTR-RD variant in trans
CF Unlikely CFTR-RD CFInconclusive
Assess for causes of false
positive sweat test (Table
2)
0 CF-causing variant
Sweat test (repeat if abnormal)
<30mmol/l 30-60mmol/l >60mmol/l <30mmol/l 30-60mmol/l >60mmol/l
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
Yes No
Sweat test (repeat if abnormal)
<30mmol/l 30-60mmol/l >60mmol/l
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
2 CF-causing variants in trans
Sweat test
Assess for causes of false
negative sweat test (Table 3)
Consultation by the geneticist
Sweat test (repeat if abnormal)
<30mmol/l 30-60mmol/l >60mmol/l <30mmol/l 30-
60mmol/l
>60mmol/l
Proceed to gene sequencing
independent of sweat test results
Gene sequencing*
0 CF-causing
variant
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)
Pseudomonas Eradication Therapy ...
... in Pregnancy?
T.G. female 36 years old
Panchaud A. et al. Respiration. 2016;91(4):333-48
Case 2
as example using the
SWISS RECOMMENDATIONSFOR 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
• Typisation du B. cepacia (Prague) : ”contaminans”
O.T. female 20 years old
O.T. female 20 years old
Table1:B.cepaciacomplexspecies(adaptedfrom1)Species Comments
B.cepacia InfectionsinCFandnon-CFpatients.Associatedto“cepaciasyndrome”B.multivorans InfectionsinCFandnon-CFpatients.Associatedto“cepaciasyndrome”
B.cenocepacia InfectionsinCFandnon-CFpatients.Associatedto“cepaciasyndrome”B.stabiliz InfectionsinCFandnon-CFpatientsB.vietnamiensis InfectionsinCFandnon-CFpatients
B.dolosa InfectionsinCFonlyB.ambifaria InfectionsinCFandnon-CFpatients
B.anthina InfectionsinCFandnon-CFpatientsB.pyrrocinia InfectionsinCFonly
B.ubonensis Infectionsinnon-CFpatientsonlyB.latens InfectionsinCFonlyB.diffusa InfectionsinCFandnon-CFpatients
B.arboris InfectionsinCFandnon-CFpatientsB.seminalis InfectionsinCFandnon-CFpatients
B.metallica InfectionsinCFonlyB.contaminans InfectionsinCFonly
B.lata InfectionsinCFandnon-CFpatients
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
Table1:B.cepaciacomplexspecies(adaptedfrom1)Species Comments
B.cepacia InfectionsinCFandnon-CFpatients.Associatedto“cepaciasyndrome”B.multivorans InfectionsinCFandnon-CFpatients.Associatedto“cepaciasyndrome”
B.cenocepacia InfectionsinCFandnon-CFpatients.Associatedto“cepaciasyndrome”B.stabiliz InfectionsinCFandnon-CFpatientsB.vietnamiensis InfectionsinCFandnon-CFpatients
B.dolosa InfectionsinCFonlyB.ambifaria InfectionsinCFandnon-CFpatients
B.anthina InfectionsinCFandnon-CFpatientsB.pyrrocinia InfectionsinCFonly
B.ubonensis Infectionsinnon-CFpatientsonlyB.latens InfectionsinCFonlyB.diffusa InfectionsinCFandnon-CFpatients
B.arboris InfectionsinCFandnon-CFpatientsB.seminalis InfectionsinCFandnon-CFpatients
B.metallica InfectionsinCFonlyB.contaminans InfectionsinCFonly
B.lata InfectionsinCFandnon-CFpatients
• 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
O.T. female 20 years old
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 C-
reactive 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“
Table4:TreatmentprotocolsusedforCepaciasyndrome(adaptedfrom9-12)
Protocolbasedon Regimen
Adultpatient,non-transplanted12
Meropenem+tobramycinIV+TMP/SMXIV+chloramphenicol+prednisolone(30-40mg)+cyclosporine50mgIV1x/dayfor5daysthen50mgorally1x/day
Atdischarge(after35days):inhaledmeropenem+cyclosporin
Adultpatient,5yearsafter
liver/pancreastransplantation10
MeropenemIV+tobramycinIV+TMP/SMXIV+temocillin+inhaledmeropenem+inhaledtobramycin
Atdischarge(after50days):inhaledmeropenemandtobramycin
Pediatricpatients(n=2)9
Case1:ceftazidime+meropenem+ciprofloxacine+chloramphenicol+TMP/SMX+methylprednisolone
Case2:ceftazidime+tobramycine+TMP/SMX+inhaledtobramycine+rhDNase
• 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
O.T. female 20 years old
CT thorax 15.8 CT thorax 16.7
CT thorax 15.8 CT thorax 16.7
CT thorax 15.8 CT thorax 16.7
• 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
O.T. female 20 years old
Table4:TreatmentprotocolsusedforCepaciasyndrome(adaptedfrom9-12)
Protocolbasedon Regimen
Adultpatient,non-transplanted12
Meropenem+tobramycinIV+TMP/SMXIV+chloramphenicol+prednisolone(30-40mg)+cyclosporine50mgIV1x/dayfor5daysthen50mgorally1x/day
Atdischarge(after35days):inhaledmeropenem+cyclosporin
Adultpatient,5yearsafter
liver/pancreastransplantation10
MeropenemIV+tobramycinIV+TMP/SMXIV+temocillin+inhaledmeropenem+inhaledtobramycin
Atdischarge(after50days):inhaledmeropenemandtobramycin
Pediatricpatients(n=2)9
Case1:ceftazidime+meropenem+ciprofloxacine+chloramphenicol+TMP/SMX+methylprednisolone
Case2:ceftazidime+tobramycine+TMP/SMX+inhaledtobramycine+rhDNase
Ourexperience Meropenem+ceftazidimeIVandinhaled+tobramycinIV+TMP/SMXoral
+tigecycline+azithromycine+prednisone(10-20mg/day)for6weeks
“Treatment of Cepacia syndrome“