Cystic Fibrosis - history

• Dorothy Anderson 1938 - documented as clinical and pathological entity all dying at 1 week+: pneumonia, purulent bronchitis, bronchiectasis & abscess

• Blackfan -main problem is inspissiated secretions

• Fanconi - lack of pancreatic enzymes lead to malabsorption; association with bronchiectasis

CF - history

• Faber 1943-45: the pathology of the pancreas is only one manifestation of the abnormality affecting all of the mucus glands

• Harry Shwachman: diagnosis based on pancreatic enzyme analysis & clinical state

• Anderson 1953 - abnormal sweat electrolytes

CF - history

• Harvey White 1958 - Children’s Memorial Hospital Chicago

• “Extensive antibiotic therapy and surgery will undoubtedly prolong life, so that we will see these children reaching their teens and young adult years with chronic pulmonary disease”

• We have now moved beyond this with increasing numbers of patients in middle age

What is cystic fibrosis?

• The most common genetic disease in caucasians

• Gene frequency - carrier status 1 in 20-25

• Autosomal recessive inheritance

• Live births in UK - approx 1 in 2000-2500

• A complex multisystem disease

How common ?Delta F508, G551D, G542X, 621+1(G>T) and

1898(G>A)

UK CF Survey

• current population in UK 8000 to 9000

• About 250 children born per year with CF

• About 150 patients with CF die each year

• Incidence showing a fall from 1:2,500 (antenatal screening, cascade screening, increased ethnic mix)

• Adult population > 50% total

What is CF?

• Affects respiration, digestion, hepatobiliary, reproductive, vascular, musculoskeletal, endocrine systems, and renal

CF

• Multisystem disease but respiratory problems account for most of morbidity and mortality

Primary cause death 1999 CFF data

Cause %Cardiorespiratory 79Transplant complic. 12Other/unknown 7Liver disease 2Suicide 1

What happens in CF?

• The lungs are normal at birth

• at post mortem - mucopurulent plugs, emphysema, collapse, pneumonia, haemorrhage

• loss of cilia, bronchial epithelial metaplasia, massive neutrophil dominated inflammatory cell infiltrate

What is CF?

• Over 90% pancreatic insufficient

• sticky secretions to blocked ducts

• secondary damage to secretory gland tissue

• digestive juices - enzymes and bicarbonate

• malabsorption, steatorrhoea, malnutrition, stunting, delayed puberty, fat sol vits

What is CF?

• CF gene causes abnormal production of the CFTR protein

• CFTR acts as a chloride channel in apical cell membrane and regulates sodium transport

• CFTR found in lungs, salivary glands, sweat ducts, pancreas, liver, reproductive tract, kidney

CFTR

• 1480 amino acids• Localizes to the apical

cell membrane• Over 1500 mutations

documented• ΔF508 is the most

common mutation in Caucasian population

• Five mutation classes

V

Alternativesplicing

3849+10kbC→T

MissenseA455E

Reducedsynthesis

IV

MissenseR117H

Alteredconductance

III

MissenseG551D

Block inregulation

II

AA deletionF508

Block inprocessing

Normal I

NonsenseG542X

Frameshift394delTT

Splice junction1717-1G→A

Nosynthesis

Molecular Consequences of CFTR Mutations

Vankeerberghen A, et al. J Cyst Fibros. 2002.http://www.genet.sickkids.on.ca/cftr/

CFTR

Pathophysiology

• CFTR expressed on the luminal surface of epithelial cells

• Impairment of function• Defective chloride transport• Increased sodium transport• Increased fluid reabsorption

• Overall increased viscosity of epithelial surface secretions

The airway cell- normal epithelial cell-

wild type CFTR

Cl-Cl

-Cl-

Cl-

Cl-

Chromosome 7

ATP

800 different mutations

glycosylation

Endoplasmic reticulum

Golgi apparatus mRNA

Impairment of CFTR function causes reduced fluid production. Enhanced sodium absorption through epithelial Na+ channels (ENaC) and

basolateral Na/K ATPase pumps results in increased fluid absorption

leading to dryer airways and impaired ciliary clearance

How does CF present to the doctor?

All pats –Meconium ileus orintestinal obstruction 19%Respiratory symptoms 52%FTT 44%Steatorrhoea 35%Family history 17%Neonatal screen 3%

Rare presenting features

• Nasal polyps/sinus disease - 5%

• rectal prolapse - 2%

• oedema - 2%

• other - male infertility, pancreatitis

At time of diagnosis

• CF is a serious disorder despite major advances in Rx and understanding

• Health now and longterm depend on effective Rx

• Outlook improves year by year

• Complex illness needing specialist care

• Sweat test sibs, “cascade screen”

CF - survival

• 1938 - 70% died in the 1st year• 2000 - 50% survive to over 30 years• Median age death 1987 to 1999, 19 to 23 yrs• Median predicted survival 1999 = 29 yrs [25.5 in

1985]• Adult [>17 yrs] USA - 1989 & 1999 31% &

38% of all patients• 2007 average survival is 39 years

MEDIAN SURVIVAL AGE FOR PATIENTS WITH CF AT VARIOUS TIMES SINCE FIRST

DESCRIPTION OF CF

Increasing survival

• >50% patients now adults (UK data)

• Median survival 38.6 years (USA data)

Median Percent Predicted FEV1 vs Age: 1990 and 2001

40

50

60

70

80

90

100

6 8 10 12 14 16 18 20 22 24 26 28 30

Age (Years)

Per

cen

t p

red

icte

d F

EV

1

1990

2001

Cystic Fibrosis Foundation. Patient Registry Annual Data Report. 2002.

Pseudomonas aeruginosa

• Wilmott 1985

• Chronic infection in 1st 5 years - 20% survival to 16 years

• No infection - 95% survival to 16 years

Survival with CF

• Many reasons for improved prognosis BUT

• survival better without chronic chest infection

• USA data 1990s: average survival with chronic PA infection = 28 years BUT without chronic PA infection = 39 years

Pseudomonas aeruginosa infection - Kerem 1990

• Life after pseudomonas in 895 patients attending Toronto clinic - At 7 years of age the mean percentage predicted FEV1 was 10% lower in children already infected compared with those who were not - p<0.01

• Throughout clinic population FEV1 in those with PA was about 10% less of predicted than those without PA

Chronic Pa Endobronchitis Is Associated with Poor Survival in CF

Henry RL, et al. Pediatr Pulmonol. 1992.

Mucoid Pa(n = 50)

Nonmucoid Pa(n = 19)

Pa-negative (n = 12)

Time (months)

Fra

ctio

n s

urv

ivin

g

0 10 20 30 40 50 60 70 80 90 100

0.6

0.7

0.8

0.9

1.0

0.5

0.4

0.0

Symptoms of infection

• Cough one of earliest and most important

• lethargy

• weight loss

• fever

• more sputum, white to yellow or green

• dyspnoea

Age-specific prevalence of infections in CF patients 2003

Cystic Fibrosis Patient Registry 2003 – Annual Data Report. October 2004.

Pathology of CF Lung Disease

Tomashefski JF, et al. The pathology of cystic fibrosis. In: Cystic Fibrosis. 1993.

At birth: lungs are normal

Disease begins in the small airways

Bronchioles fill with chronic mucopurulent material

Childhood and adolescence: progressive loss of small airway function

Structural Changes Occur Even in Mild CF Lung Disease

• 60 children with CF (6-12 years old)

• Mean FEV1 = 102% predicted

• 11/37 patients with normal lung function (all PFT values >85% predicted) had HRCT evidence of bronchiectasis

Brody AS, et al. J Pediatr. 2004.

• FEV1: 91% of predicted• FVC: 95% of predicted• FEF25-75: 89% of predicted

CT Scans of Normal and CF Lungs

Normal CF

Tiddens HA. Pediatr Pulmonol. 2002.http://www.rrcc-online.com/paprogram/HISTHTML/RADNORM/CHCT02.HTM.

The Vicious Cycle of CF Lung Disease

Chmiel JF, et al. Clin Rev Allergy Immunol. 2002.

Inflammation

Obstruction

Infection

•Airway clearance•Dornase alfa•Hypertonic saline•Bronchodilators

•Ibuprofen•Corticosteroids

•Tobramycin•Azithromycin

Treatment of the chest in children with CF - 1st principle

• PREVENTION

• PREVENTION

• PREVENTIONPREVENTION

Pseudomonas aeruginosa: Sources in the Healthcare Environment

• Recovered from toys, baths, soaps, nebulizers, sink drains, and hands of patients and staff

• Nonmucoid strains can survive for 24 hours, mucoid strains for ≥48 hours

• On dry surfaces, pathogens suspended in sputum can live for up to 8 days

Saiman L. et al. Clin Microbiol Rev. 2004.

P aeruginosa: Patient-to-Patient Transmission

• Shared strains found in Germany, United Kingdom, Australia, Denmark, and United States• Linked to antibiotic resistance• May involve transmission from Pa-positive to Pa-

negative patients

• Documented between siblings with CF• Linked to summer camps• Possibly via contaminated environment

Saiman L. et al. Clin Microbiol Rev. 2004.

Modes of Transmission

• Direct: body-to-body surface transfer• Kissing• Touching• Patient care• Shaking hands

• Indirect: contact with a contaminated object• Toys• Shared toothbrushes• Eating utensils• Gloves• Respiratory equipment

Saiman L. Cystic Fibrosis Foundation [webcast]. 2004.

Droplet Transmission

• Person-to-person spread by droplets of infected secretions

• Droplets travel short distances (<3 feet)

• Pathogens within droplets can live for hours on surfaces

Saiman L. Cystic Fibrosis Foundation [webcast]. 2004.

http://phil.cdc.gov [picture].

Control and treatment of infection

• Strict infection control measures• Side rooms for admission• Segregation according to sputum microbiology

• Microbiological surveillance• Sputum microbiology regularly• Serum Pseudomonas antibodies

Reducing the risk of Ps infection

• Centre B

• young patients integrated with older Ps +ve patients

• older hospital

• smaller waiting room

• 1 doctor, 2 nurses

• therefore waiting longer - more exposure

Make life more pleasant on the ward

• Allow individual patients to use rooms off the ward with their own friends and families

• These times can be reserved

Make life more pleasant

• Fridge

• TV/Video/DVD

• Have a ward video/DVD library

• Sky TV

• Computer with internet access and webcam

• Flexibility about “time out”

Paediatric wards

• Children need to be:• kept busy

• treated with respect

• their sense of freedom preserved

• able to socialise and communicate with peers

To achieve these aims on paediatric wards

• Discuss problems with parents and ask for their help

• Encourage family and friends to • visit in small groups or on own• to visit more often and for longer• to take child out between treatments

• Free passes to variety of local entertainments and information “what’s on”

Eradication regimens for 1st & intermittent Ps aeruginosa

• Copenhagen centre 1997 -

“temporary postponement (of pseudomonas infection) may add a significant number of disease-free years to the life of the individual with CF”

Prevention of chronic Ps aeruginosa infection

• 26 patients with no previous anti-pseud. Rx

• Ps aer isolated: a] bd ciproxin 250-750 mg b] bd nebulised colomycin 1 MU

• Rx repeated at each +ve isolate

• Chronic infection = culture 6 consecutive months or +ve precipitating antibodies

Prevention of chronic Pseud infection

• 27 months trial

• 7 [58%] of 12 untreated – chronic infection

• 2 [24%] of 14 treated – chronic infection

• P<0.05

• Further studies show Rx for 3 months with cipro & colo eradicates infection in 80%

Eradication protocols

• We do not know – optimal antibiotic combination, dosage, or duration of treatment for PA eradication

• Other regimens than the Copenhagen protocol may be as, or more, successful

Gibson et al 2003

Eradication protocols - TOBI?

• Children < 6 yrs with early PA infection received 300 mg TOBI or placebo bd 28 days; repeat BAL same lobar segment

• Day 28 – all 8 TOBI children PA –ve 12/13 placebo children +ve trial stopped

Ratjen et al, Lancet 2001

Eradication protocols• Other protocols also successful

• Ratjen et al 2001:

1st PA treated with nebulised tobramycin 80 mg bd for 1 year

14/15 patients PA –ve after 1 yr treatment and remained PA –ve at 1 year follow-up visit

*Taccetti, Eur Resp J 2005; **Munck, P Pulmonol 2001

Eradication protocols• Taccetti* and Munck** showed about 75% of

reinfections were with unrelated PA genotype

• Therefore showing true eradication

Effect of cohort isolation 1981 & early treatment 1989

• Annual incidence PA infection: intermittent 32% to 17%,

chronic 16% to 9%• 1st to chronic PA from 1 to

4 yrs i.e. cohort isolation alone can delay chronic PA

• Early treatment 1989: • incidence chronic PA

infection fell to under 2% per year

Reduction in prevalence of chronic PA infection in Leeds

• 1975 - neonatal screening & regular microbiological surveillance

• 1985- early nebulised antibiotic treatments of 1st isolates of PA

• 1988 - intensive IV antibiotic treatment where nebulised therapy failed to eradicate PA

• 1991- separate clinics for PA culture +ve & improved hygiene in purpose built centre

PA data - Jan 1990 to Dec 2000

• Prevalence of chronic infection fell from 25% to 18%

• In children < 11 years prevalence fell from 24% to 4% (p<0.02)

• Over 11 years of age prevalence rose from 31% to 38% but mean age of this group up from 12 to 14 years

Data 1990-2000

• Yearly prevalence for intermittent infection rose from 26% to 35%

• Over 11 year period 85 children had 1st PA sputum culture. Eradication therapy failed in 3. Mean time to 2nd isolate was 25 months

• Free of PA (no growth > 1 year) rose from 21% to 27%

0

2

4

6

8

10

12

14

Patientnumbers

0-4 49-50 105-08

Months until regrowth of PA after eradication treatment (black) or still no regrowth(grey)

CHRONIC

0

5

10

15

20

25

30

35

40

45

1990-2000

% o

f clin

ic

Eradication therapyincreased to 3 months

FREE

0

5

10

15

20

25

30

35

40

45

1990-2000

% o

f clin

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Eradication treatmentto 3 months

Mean age of Incidence of Chronic P. aeruginosa Infection

0

2

4

6

8

10

12

14

16

1990 - 2000

Mea

n ag

e (y

ears

)

Growing up without PA in LeedsAll full care children (%)

Children < 11 years (%)

N 145 (100) 69 (100)

Chronic 18 (12) 5 (7)

Intermittent 47 (32) 18 (26)

Free > 1 year 49 (34) 25 (36)

Never 31 (21) 21 (30)

Adult Leeds Clinic

• 317 patients

• PA infection status

• chronic – 169 (53%) intermittent – 58 (18%) no PA – 90 (29%)

Conclusion

• In patients with CF chronic PA infection is not inevitable

Use of IV antibiotics

• To eradicate early Ps infection

• to treat new cough not settled with oral Rx

• to treat a respiratory exacerbation

• routine 3 monthly?

More frequent Iv Rx for Ps aeruginosa - Copenhagen

• 1971-5: treated only in exacerbation

• 1975-80: treated every 3 months

• 5 year survival from time of onset of chronic infection: 1971-75 – 54% 1975-80 – 82% p<0.05

• Disadvantage: high cost, resistance, allergy

Established PA infection

• 3 monthly intravenous antibiotic courses - or not?

• Nebulised anti-pseudomonal antibiotics?

• New vibrating mesh nebulisers

• AAD devices

• Dry powder inhalation

• Pulmozyme?

Nebulised anti-pseudomonal antibiotics

• YES - better lung function, slower fall in lung function, less hospital admissions, better weight, better clinical score, lower sputum PA density

Pulmozyme

• Should be tried in all children with signs and symptoms of lower respiratory infection and inflammation - sputum production, chronic cough

• Will not work in all.

• Used to suggest 1 month trial and endpoint of at least 10% improvement in respiratory function

• Recent multi centre study 6-11 year olds

Prevention

• Prompt treatment of respiratory exacerbations - Pond 1996

• Exacerbation = 10% decrease in respiratory function or increase in severity of 2 or more LRT symptoms

• Post-treatment lung function almost identical to pre-treatment values

• Properly treated exacerbations are short-term dips on background trend

Burkholderia cepacia

• A plant pathogen – soft rot in onions

• Ubiquitous- especially in association with water, soil, plants

• Less common than Ps aeruginosa

• Inherent antibiotic resistance

• 1st report in CF 1977 in Philadelphia

• Concerns: outcome, person to person spread

Treatment - Staph. aureus

• Prophylactic or intermittent?

• 1994- Weaver:

• 38 screened infants - episodic or continuous

• Treatment group:

• < cough [2% v 12%]

• < inpatient days [5 v 19]

Anti-staphylococcal therapy

• Treatment group had

• less frequent cough

• less SA URT isolates, 17% v 60%, p<0.01

• less hospital admissions in 2nd year, 19 v 5

• shorter admissions, 2 v 6 days

• less antibiotic courses per year, 4 v 8

• Improved clinical progress in 1st 2 years

Staphylococcal therapy

• Cochrane review: no certainty that use after 2 years of age is beneficial

• concern re-development of MRSA, more likely to acquire PA, expense

• Do we have a problem with MRSA or PA in Leeds?

• Are we aware of significant S. aureus effects?

Patient A - 4 years old

• Diagnosis at 9 months

• no antibiotics

• weight and height 0.4th centile

• clubbing marked & lower zone crackles

• frequent cough, cough with activity, yellow-green sputum

• ONLY ISOLATE = STAPHYLOCOCCUS

Patient B - age 29 years

• Occasional cough

• sputum 0-50 mls/day yellow-green

• FEV1 20-50%

• FEV1 1995 = over 4.0L

• FEV1 1999 = 1L-2.0L

• SPUTUM ISOLATE = STAPHYLOCCUSONLY

Methicillin-Resistant Staphylococcus aureus (MRSA)

• National rate: 6%1

• Range: 0% to 19.3%

• MRSA associated with worse chest x-rays, poor growth, greater need for antibiotics, and trends toward lower PFT2

• Vancomycin or linezolid used to treat/eradicate MRSA in CF3,4

1Cystic Fibrosis Foundation. Patient Registry Annual Data Report. 2000.2Miall LS, et al. Arch Dis Child. 2001.

3Solis A, et al. Pediatr Pulmonol. 2003. 4Ferrin M, et al. Pediatr Pulmonol. 2002.

0

5

10

15

20

25

30

CF Centers

% P

reva

len

ce

Other prophylactic treatment

• Management of other viral respiratory infections - “colds”

• additional antibiotic with every “cold”

• need to cover streptococci, H. ‘flu, opportunistic Ps infection, possibly atypical organisms

• close review & early IV treatment if not settling

Viral type infections

• Copenhagen data 1965-1990

• 66% got 1st PA and 68% chronic PA during winter months Oct- March, the viral season

• Therefore: Optimise vaccination opportunities Screen for viral infection Intensive surveillance and treatment of children with viral infection

New pathogens

• Atypical mycobacteria

• Fungal – scedosporium, exophiala

• Alcaligenes

• Stenotrophomonas maltophilia

Aspergillus

• Allergic bronchopulmonary aspergillosis (ABPA)• 10% of RTE in CF

• Can cause severe infections after transplant

• Comes from the environment, not spread from person to person

Moss RB. Clin Rev Allergy Immunol. 2002.Gibson RL, et al. Am J Respir Crit Care Med. 2003.

Saiman L, et al. Infect Control Hosp Epidemiol. 2003.

Consensus Conference Diagnostic Criteria for ABPA in CF

• Clinical deterioration • Cough, wheeze, exercise intolerance/bronchospasm, ↓ PFT,

↑ sputum

• Serum IgE >1000 IU/mL (~2400 ng/mL)• Immediate skin test reaction to Aspergillus or A

fumigatus serum IgE antibodies• Serum A fumigatus–specific IgG antibodies• Abnormal chest radiograph or CT

• Infiltrates, mucus plugging, or change from previous imaging study

Stevens DA, et al. Clin Infect Dis. 2003.

Nontuberculous Mycobacteria

• Prevalence 7% to 24%; increases with age • M avium complex (72%), M abscessus (16%)• Some CF patients at risk for clinical decline

• Steeper rate of decline; higher prevalence of S aureus

• Suggestive of infection: multiple positive AFB smears or granulomatous disease

• At least 1 year of treatment with multiple antibiotics

• Not transmitted from person to person

Olivier KN. Paediatr Respir Rev. 2004.Gibson RL, et al. Am J Respir Crit Care Med. 2003.

Home intravenous therapy

• Convenience

• Safety

• Back-up

• Make as easy as possible

• Intravenous access devices

Gastrointestinal Disease in Cystic Fibrosis

Gastroesophageal reflux

Pancreatic insufficiencyPancreatitis

Meconium ileusDIOS

Rectal prolapse

Intussusception

Hepatobiliary disease

Small bowel overgrowthFibrosing colonopathy

Enteral tube feeding

• Patients unable to achieve or maintain adequate energy intake or growth even with high fat diet and oral supplements

• Fail to achieve wt gain over 6 months

• wt/ht < 90%

• BMI [kg/m2] <19 in adults

• Significant wt loss in acute exacerbation

• Poor weight gain in pregnancy

Lung Transplant

• Only 40% on list will get a transplant

• Living related donor transplants

• It is not a cure

• It can go wrong early and late

Obliterative bronchiolitis

• Madden 1992: found in 17%, 23% and 48% at 1, 2, and 3 years post-op

• Mendeloff 1998: found in 37% and 57% at 2 and 3 years post-op

Transplant - our figures

• 31 patients

• Mean age at operation - 24 years

• Mean FEV1 - 23% predicted

• 19 alive with mean FEV1 - 72% predicted

• 3 died early

• Mean age death late - 996 days

• Actuarial survival 87%, 76%, 58%, 47% at 1, 2, 6, 10 years

Complications

• Liver disease

• Diabetes mellitus

• Arthritis

• Osteoporosis

• DIOS

Liver disease

• Initial diagnostic finding in 1.5%• Cause death in 2.2%• Peak incidence in adolescence• Abnormal bile flow & inspissated secretions

secondary to defect in chloride transport• Mild & asymptomatic focal biliary

cirrhosis with hepatosplenomegaly, varices

Liver disease

• Screening: clinical, LFTs, US, DSIDA

• Treat: early with UDCA, Taurine

CF and diabetes mellitus

• Must screen with OGTT when clinically stable

CFRD

• Increased prevalence [ up to 53%]

• Associated with worse pulmonary outcome.

• Early diagnosis critical.

• OGTT - Gold standard for diagnosis.

• Annual screening recommended in all patients > 10 years of age.

ANNUAL INCIDENCE DIABETES

8.98.2

3.3

6.3 6.7

0123456789

10

1995 1996 1997 1998 1999

% incidence

PREVALENCE DIABETES

12

2326

2830

0

5

10

15

20

25

30

35

1995 1996 1997 1998 1999

% prevalence

Complications

• Liver disease

• Diabetes mellitus

• Arthritis

• Osteoporosis

• DIOS

INVESTIGATIONS - AXR

• Faecal loading in RIF• Dilatation of ileum• Empty distal colon• Fluid levels and

variable degree small bowel dilatation may be seen during acute attack

INVESTIGATIONS – AXR

• Faecal loading RIF• Granular/bubbly in

appearance

Other complications• Renal dysfunction

• Related to CFRD and long term aminoglycoside and polymixin use

• Neurological• Hearing loss secondary to aminoglycoside• Neuropathy secondary to diabetes and polymixin use

• Psychosocial• Depression, anxiety, adherence problems

• Oncological• Increased risk of GI malignancy• Increased malignancy post transplant

• Drug allergies

TREATMENT BURDEN

• Lot of treatment• Physiotherapy

• Nebulised/Inhaled drugs

• Oral treatment

• Insulin

• Intravenous antibiotics

• Liver drugs

• Vitamins

• Overnight feeds

• Oxygen

Treatment burden

Paediatric CF

• Most children should not cough

• Most children miss no school

• Most children play games and sport like all other children

Neonatal screening

• In Leeds from early 1980s

• Now national programme rolling out

• Based on IRT test on 6 day Guthrie sample

CF - treatment

• Better survival reflects

• better antibiotics

• better physiotherapy

• better nutrition

• care in CF centres

CF – intensive therapy & better survival

• 3 CF centres 1971-80 with median survival of 9.5, 18.1, 22.8 years

• Mean number OPD visits: 4, 8, 12 per year

• Mean hospital days: 4.7, 5, 9.5 per year

• % admitted at least x1 per year: 19, 21, 31

• Survival correlates strongly with intensive antibiotic use

The comprehensive CF assessment

• “success of treatment will depend on a complete assessment of the patient and then continuing attempts to obtain normal bodily function and maintain it” [Crozier 1974]

• every new patient

• every patient annually

The CF assessment

• History - including immunisation, smoking, sibs sweat tested, cascade gene screening

• Examination with height and weight

• RFT, bronchodilator reversibility

• Physiotherapist and dietician assessment

• Social worker contact

The CF assessment

• CXR, AXR, abdo US if >10 yrs old

• Sputum, cough swab, [sweat test/gene screen]

• FBC, PV, CRP, U&E, LFT, HbA1c [if DM], fat soluble vits, PT

• IgE, IgG, Aspergillus pptns, RAST, Ps antibodies

• Faecal fat microscopy

Multidisciplinary Team

• Doctors Nurses• Physiotherapists Dietitians• Social workers Psychologists• Pharmacist Microbiologist

• Plus close links with O&G, rheumatology, surgery, radiology, gastroenterology, hepatology

Role of the GP

• Most GPs only 0-1 patients with CF

• Diagnosis - support

• Prescribing routine treatment, at least month’s supply

• Check all immunisations done

• Antibiotics with URTIs

• Initial assessment for intercurrent illness

• COMMUNICATION - 2-WAY

Therapeutic Approaches for CF Lung Disease

Adapted from Weinberger SE. N Engl J Med. 1993.

Gene therapy

Defective

gene

Defective

protein(CFTR)

*Cl-

Abnormal epithelial ion transport

ATP, UTP Amiloride Dornase alfa

Viscous intraluminal secretions

Airway clearancetechniques

Oral, aerosol,

andIV antibiotics

Release of DNA and F-actin from degraded cells

Irreversiblelung injury

Lung transplantation

CorticosteroidsIbuprofen

Accumulation of inflammatory cells

and release of proteolytic enzymes

Chronic bacterial infection

“Viscouscycle”