SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE · SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE Dr Christian MURER (University Hospital, Zürich) Urs BÜRGI (University Hospital,

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


• 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


• 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 ?


• 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


• 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.


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)


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)


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


Case 1

as example using the


• 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.


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.


Lung function

• Severe Obstruction,

FEV1 49% pred. (1.49 l)

• Air Trapping

• DLCO 78% pred.

• FeNO 14 ppb


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


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


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

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


<30mmol/l 30-60mmol/l >60mmol/l


negative sweat test (Table 3)

Consultation by the geneticist

2 CF-causing variants in trans

Sweat test





<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


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


positive sweat test (Table

2)

0 CF-causing variant


<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


<30mmol/l 30-60mmol/l >60mmol/l




2 CF-causing variants in trans

Sweat test





<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?


Panchaud A. et al. Respiration. 2016;91(4):333-48

Case 2

as example using the


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”



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”).



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


Rx thorax 4.7

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


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.


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

Ourexperience Meropenem+ceftazidimeIVandinhaled+tobramycinIV+TMP/SMXoral

+tigecycline+azithromycine+prednisone(10-20mg/day)for6weeks

“Treatment of Cepacia syndrome“

Documents

SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE · SWISS RECOMMENDATIONS FOR ADULT CF PATIENT CARE Dr Christian MURER (University Hospital, Zürich) Urs BÜRGI (University Hospital,