cystic fibrosis 1

Case presentation

case• 8 months y/o girl, from Arar, SVD, Full term.• presented to the Ped- ER with SOB, Cough and

diarrhea since 4 months Pre time of first admission in KFMC 2011.

• Cough was sever inter fir with her sleeping and feeding, increase with breast feeding, with no specific reliving factors.

• Diarrhea since birth wax and win, grassy and offensive, frequent 3 time/ day

• ROS.▫Wt loss, decrease appetite.

• PMH▫Recurrent admission in local hospital due to

recurrent chest infection, Mx by Abx.• No PSH• Developmental Hx :

▫upto her age • Family Hx

▫1° consinguity▫The first baby girl dead at age of 4 month with

similar presentation.▫No family Hx of inherited disease nor congenital.

• Socioeconomic status ▫Fair

O\E •She very thin with loss of adipose tissue ,

distressed, not cyanotic no dimorphic feature. With good suckling.

•Vitally : tackyapnic on 0.25 L O2 nasal cannula.

•Wt= 4.6 kg Ht= 60 c.m (below the 3rd percentile) •Heart: S1+S2 no add sound nor murmur •Chest : bilatral crakles •Abd: soft and lax •Neurological : inact

First Impression •C.F•I° Immunodeficiency •Aspiration syndrome

Significant finding on paraclinical • CBC

WBC = 11.3 lymph = 6.82% U&E

Albumin = 31 g/lProtein = 63 g/lESR= 19 ŊImmunological study within normal Chloride sweat test (61- 80)

1° 102 mmol/l2° 113 mmol/l

Pancreatic enzyme on Faecal <50 ug/g

CXR

Swallowing test

Definitive diagnosis C.F •Genetic study done

▫Homozygous single nucleotide deletion ▫In chromo 11 of the CFTR

Cystic Fibrosis

Presented by:Sheikah A. Bawazir

Objective •Genetic aspect•Path physiology•Presentation •diagnosis •Management •Futuer

•Cystic Fibrosis (CF) is a lifelong, hereditary disease that causes thick, sticky mucus to form in the lungs, pancreas, and other organs . In the lungs, this mucus blocks the airways, causing lung damage, making it hard to breathe, and leading to serious lung infections . In the pancreas, it clogs the pathways leading to the digestive system, interfering with proper digestion .

• In 90 percent of cystic fibrosis cases, the airways are affected .

Epidemiology •Common in Caucasians •1:2000-3000 live births•M=F•Typically presents in childhood

▫7% of CF patients diagnosed as adult•Most common cause of sever ch.lung

disease among pediatric group.•Increase life expectancy from 6 months in

1960 to near 40 years now a days

Genetic aspect•Autosomal recessive •Mutation in the CFTR gene•On q31.2 locus, long arm of chromosome

7•Most of people have 2 copies .•1500 mutation that can produce C.F•Most common mutation is ΔF508.•In 66%-70% of C.F cases.•carrier rate =1/25

Autosomal recessive

Pathphysiology •Disease of exocrine glands cause abnormal

transport of Cl and Na across an epithelium , leading to thick, viscous secretions

•different mutations cause different defects in the CFTR protein

•causing a milder or more severe disease

•Other mutations in the CF gene produce fully processed CFTR proteins that are either non-functional or partially functional

• DF508 mutation leads to improper processing and intracellular degradation of the CFTR protein

Lung

• Gastrointestinal▫Pancreas

Absence of CFTR limits function of chloride-bicarbonate exchanger to secrete bicarbonate

Leads to retention of enzymes in the pancreas, destruction of pancreatic tissue.

▫Intestine Decrease in water secretion leads to thickened mucus and

dessicated intraluminal contents Obstruction of small and large intestines

▫Biliary tree Retention of biliary secretion Focal biliary cirrhosis Bile duct proliferation Chronic cholecystitis, cholelithiasis

• Sweat▫Normal volume of sweat▫Inability to reabsorb NaCl from sweat as it

passes through sweat duct

Manifestation •Common presentations

▫Chronic cough▫Recurrent pulmonary infiltrates▫Failure to thrive ▫Meconium ileus

Genitourinary Gastrointestinal Respiratory tract

Pseudo bartter’s

Late onset puberty

Due to chronic

>95% of male patients with CF have azospermia

20% of female patients with CF are infertile

>90% of completed pregnancies produce viable infants

Meconium ileus

distal intestinal obstruction syndrome

Exocrine pancreatic insufficiency

Found in >90% of CF patientsdecreases with age

Increased incidence of GI malignancy

Chronic sinusitisNasal obstructionRinorrheaNasal polyps in 25%

Chronic coughPersistentViscous, purulent, green sputum

Diagnosis•DNA analysis not useful due to large

variety of CF mutations

•Sweat chloride test >80 mmol/l 1-2% of patients with clinical manifestations of

CF have a normal sweat chloride test•72 hr. fecal fat determination

•Sputum culture (to ID infective organisms)

Diagnosis•Criteria

▫One of the following Presence of typical clinical features History of CF in a sibling Positive newborn screening test

▫Plus laboratory evidence for CFTR dysfunction Two elevated sweat chloride concentrations on two

separate days Identification of two CF mutations

Treatment•Major objectives

▫Promote clearance of secretions

▫Control lung infection

▫Provide adequate nutrition

▫Prevent intestinal obstruction

A Vicious Cycle

ASPIRATION

ASTHMA

ASPERGILLOSIS

CYSTICFIBROSISGASTRO-

ESOPHAGEALREFLUX

PRIMARYCILIARY

DYSKINESIA

NEURO-MUSCULARWEAKNESS

CYSTICFIBROSISChomp.

Interrupting the Vicious Cycle

ANTIBIOTICS

Treatment• Lung

▫Antibiotics Early intervention, long course, high dose Staphylococcus- Penicillin or cephalosporin Pseudomonas treated with two drugs with different

mechanisms to prevent resistance e.g. cephalosporin + aminoglycoside

Use of aerosolized antibiotics Oral cipro for pseudomonas

Rapid emergence of resistance Intermittent treatment (2-3 weeks), not chronic

IV antibiotics for severe infections or resistant to orals

Pseudomonas aeruginosa

Interrupting the Vicious Cycle

ANTIBIOTICS

AIRWAYCLEARANCETECHNIQUES

Treatment•Lung

▫Breathing exercises▫Flutter valves▫vest machine▫Chest percussion▫Hypertonic saline aerosols

Interrupting the Vicious Cycle

ANTIBIOTICS

ANTI

-

INFLAM

MATOR

IES

AIRWAYCLEARANCETECHNIQUES

MUCOLYTICS

BRONCHODILATORS

Treatment•Lung

▫Increasing mucus clearance Sulbetamole + HTS + CPT Long-term DNAse treatment increases time

between pulmonary exacerbations

▫Anti-inflammatory Flixotide

Treatment•Lung

▫Atelectasis Chest PT + antibiotics

▫Respiratory failure and cor pulmonale Vigorous medical management Oxygen supplementation Only effective treatment for respiratory

failure is lung transplantation 2 year survival >60% with lung transplatation

Treatment•Nutrition

▫Pancreatic enzyme replacement

▫Calories  ranging from normal to 150 %

▫Replacement of fat-soluble vitamins- especially vitamin E & K

Treatment•Gastrointestinal

▫Insulin for hyperglycemia▫Intestinal obstruction

Pancreatic enzymes + osmotically active agents Distal- hypertonic radiocontrast material via enema

▫End-stage liver disease- transplantation 2 year survival rate >50%

▫Hepatic and gallbladder complications treated as in patient without CF

Back to Our case•Gentamicin and tazocin•Pancreatic enzyme•Ventolin + HTS+ CPT•ADEK•Vit.D•Nacl and Kcl oraly •Follow up app. 2 month

Pt readmitted multiple time due to pul. Exacerbation ,pseudo bartter's FTT.

17 month

21 month

22 month

34 month

42 month

48 month

5.56

6.57

7.58

8.59

9.510

10.511

11.512

5.8

6.6

7.5

8.4

10.310.7

6.5

7.27.8

9.33

10.8

11.8

weight on discharge

NGT over night feeding Omeprezole started

GT tube

Last admission

C.F. Future • Journal of Cystic Fibrosis Volume 10 Suppl 2

(2011) S114–S128Gene and cell therapy for cystic fibrosis: From

bench to bedside

• Ivacaftor ▫ is approved for use in cystic fibrosis patients in the US and across some

European countries. The US Food and Drug Administration approved Ivacaftor in January 2012

▫ During Phase 3 clinical trials, the STRIVE study demonstrated a 10.6% mean absolute improvement in baseline lung function (FEV1) over a 24 week period and a 10.5% mean absolute improvement in lung function over 48 weeks among those who had the G551D mutation and were treated with Ivacaftor

▫ Cystic Fibrosis Trust Research Strategy 2013–2018 in UK

Summary

Reference •  Yankaskas JR, Marshall BC, Sufian B, Simon RH, Rodman D. (2004). 

"Cystic fibrosis adult care consensus conference report". Chest 125 (90010): 1–39.doi:10.1378/chest.125.1_suppl.1S. PMID 14734689

• U .S . Census Bureau . The 2010 Statistical Abstract . Population: Estimates and Projections by Age, Sex, Race/Ethnicity . Table 6 . Available at http://www .census .gov/compendia/statab/cats/population/estimates_and_projections_by_age_sex_raceethnicity .html . Accessed January 7, 2010 .

• Centers for Disease Control and Prevention . National Center for Health Statistics . CDC Wonder On-line Database,

• compiled from Compressed mortality File 1999-2006 Series 20 No 2L, 2009 . Accessed January 11, 2010

• Cystic Fibrosis Foundation . Patient Registry 2007 Annual Report . September 2009 . Available at http://www .

• cff .org/research/ClinicalResearch/PatientRegistryReport/ . Accessed January 11, 2010• http://www.uptodate.com/contents/cystic-fibrosis-antibiotic-therapy-for-lung-disease#H13• http://www.uptodate.com/contents/cystic-fibrosis-overview-of-the-treatment-of-lung-disease?sourc

e=see_link&anchor=H12#H12• Long-term daily high and low doses of azithromycin in children with cystic fibrosis: A

randomized controlled trial.S.K. Kabra, , R. Pawaiya, Rakesh Lodha, Arti Kapil, Madhulika Kabra, A. Satya Vani, G. Agarwal,,S.S. Shastri,DOI: 10.1016/j.jcf.2009.09.001, http://www.sciencedirect.com/science/article/pii/S1569199309001234

• http://www.uptodate.com/contents/cystic-fibrosis-nutritional-issues