Risk Factors Associated with Clinical Outcomes of

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Risk Factors Associated with Clinical Outcomes
of Cystic Fibrosis
Hui-Chuan Lai, Ph.D, R.D. Department of
Nutritional Sciences University of Wisconsin -
Madison
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Cystic Fibrosis Facts
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Cystic Fibrosis - Genetics
?F508
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defected CFTR protein ? abnormal salt transport ?
production of abnormally thick, sticky mucus ?
blocks ducts and disrupt normal functions of
many organs
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Clinical Manifestations
GI System pancreatic insuf. meconium ileus
Cystic Fibrosis
Other diabetes liver disease
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Diagnosis and Treatment
Diagnosis
- Because of symptoms, positive family history
or via neonatal screening
- Dx confirmed by sweat test and/or CFTR
mutation analysis
Treatment
- In specialized regional CF centers
- Focus on improving nutritional status and
controlling lung disease
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CF Disease Progression
Pul fail. ?
Tx ?
Gene thrpy ?
TOBI DNase ?
Ab ?
Hospitalization
? Enz Diet
CPT ?
? SF
? Enz
? Insulin
delay
Dx
?What determines progression???
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Measures of CF Progression
Malnutrition
- Growth, biochemical, dietary
Lung disease
- PFT, CXR, infection, hospitalization
Prognostic scores
Quality of life (QOL)
Survival
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Potential Risk Factors
Disease
Genotype Phenotype
Demographic
Management
Malnutrition Lung disease
Gender Age
Diagnosis Therapy
Survival
QOL
?Evidence from epidemiological studies
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Gender Gap in CF
? ? ?

• Survival

• Lung disease

? ? x

• Malnutrition

? ? x
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Survival Females worse than Males
US
Canada
(AJE 19961431007)
(CFF Annual Report, 1998)
UK
Australia
(BMJ 1989298483)
(Ped Pul 19873288)
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Lung Disease Females worse than Males
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Malnutrition opposite trends
(AJCN 199969531)
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Diagnosis Females later than Males

(AJE 2002156165)
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Genotype
Severe vs. mild mutations
(?F508, Class IV/V mutations)

• Survival

?

• Lung disease

? x

• Malnutrition

? ? ?
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Severe vs Mild Mutations
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Major Phenotypes

• Survival

??

• Survival

??

• Lung disease

??

• Lung disease

??

• Malnutrition

• Malnutrition

??
? ?
PS patients live longer, have milder lung disease
and malnutrition than PI patients
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Meconium Ileus (MI) and Survival
SCREEN
Survival probability
MI
FH
O.R. P-value MI 1.80 .001 FH
1.46 .046 SYMP 1.76 .001
SYMP
Age (years)
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Meconium Ileus (MI) and Nutritional Status
(Lai et al, Pediatr 2000)
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Diagnosis
Early vs. late (neonatal screening)
?

• Survival

• Lung disease

? ?

• Malnutrition

???
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Neonatal Screening Prevents Malnutrition
(Pediatr20011071)
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Therapy
Treatment side effects

• Survival

?

• Lung disease

?
? ?

• Malnutrition

- corticosteroids
- antibiotics
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Chronic Prednisone Therapy Impairs Growth
(NEJM2000342851)
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Factors Determining Progression
Disease
Genotype Phenotype
Management
Demographic
Malnutrition Lung disease
Diagnosis Therapy
Gender Age
Survival
QOL
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Inter-relationships Between Malnutrition and
Lung disease
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Malnutrition and Survival
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Malnutrition and Lung Disease
(Pediatr Pulmonol Suppl 200020A506 )
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Lung Disease and Survival
- single most significant predictor of
survival in epidemiological studies
P. aeruginosa infection
- rate of FEV-1 decline accelerates with
acquisition of P. aeruginosa
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CF Epidemiological Research Opportunities and
Challenges

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Population Data CF Registries

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Challenges in Longitudinal Analysis

PFT
Dietary intake
CXR
Growth
Age
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Challenges in Time-to-Event Analysis
no data
L-truncation R-censoring
Dx
-Evt
Br
Dx
Evt
Br
L-censoring
Dx
Evt
Br
Int-censoring
Dx
Evt, ?age
Br
Recurrent events
Dx
Evt
Br
-Evt
Evt
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Develop Tools to Facilitate Clinical Care
The QuICC History
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Acknowledgements
CF Center directors and coordinators (who make
national registries such a valuable resource
for CF care and research)
Collaborators UW-Madison - PM Farrell, MJ
Rock, MR Kosorok, T Cook US Cystic Fibrosis
Foundation - S FitzSimmons, P Campbell
Canadian Cystic Fibrosis Foundation - M Corey
Johns Hopkins University School of Medicine -
B Rosenstein