Overview/Definition
Definition:
• Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CFTR gene, resulting in defective chloride transport and multisystem disease affecting primarily lungs, pancreas, and digestive system
Life-limiting condition requiring early diagnosis through newborn screening and comprehensive multidisciplinary management including novel CFTR modulator therapies.
Epidemiology:
• Incidence varies by ethnicity: 1 in 3,500 births in Caucasians, 1 in 15,000 in African Americans, 1 in 100,000 in Asian populations
In India, estimated incidence 1 in 40,000-100,000 births with under-diagnosis due to lack of universal screening
Carrier frequency approximately 1 in 25 in Caucasian populations.
Age Distribution:
• Symptoms can present at any age but majority diagnosed in first year of life through newborn screening programs
Classic presentation includes meconium ileus (15-20% of newborns), failure to thrive, recurrent respiratory infections, and pancreatic insufficiency
Late diagnosis possible with milder mutations or atypical presentations.
Clinical Significance:
• Critical high-yield topic for DNB Pediatrics and NEET SS examinations focusing on screening protocols, genetic counseling, comprehensive care, and breakthrough CFTR modulator therapies
Essential for understanding precision medicine approaches, multidisciplinary care coordination, and family-centered chronic disease management in pediatric practice.
Age-Specific Considerations
Newborn:
• Newborn screening using immunoreactive trypsinogen (IRT) identifies most CF cases before symptoms develop
Meconium ileus present in 15-20% of CF newborns requiring immediate surgical consultation
Pancreatic insufficiency present in 85-90% from birth requiring enzyme replacement
Early nutritional optimization critical for long-term outcomes.
Infant:
• Peak age for CF diagnosis through screening follow-up or symptomatic presentation
Failure to thrive, chronic cough, recurrent respiratory infections, and bulky stools common presentations
Airway clearance techniques adapted for infants
Nutritional requirements 120-150% of normal due to malabsorption
Growth velocity monitoring essential.
Child:
• School-age children require intensive daily management including airway clearance, medications, and nutritional support
Pulmonary function testing becomes possible for monitoring disease progression
Chronic colonization with CF-specific pathogens develops
Social challenges including treatment burden, school absences, and peer relationships.
Adolescent:
• Transition period with increased responsibility for self-management and treatment adherence challenges
CFTR modulators may be available based on genotype
Fertility counseling important as males typically infertile
Preparation for adult care transition
Psychosocial support crucial for adaptation to chronic illness.
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Clinical Presentation
Symptoms:
• Respiratory: chronic productive cough, recurrent pneumonia, persistent sinus congestion, nasal polyps
Gastrointestinal: bulky greasy stools, poor weight gain despite good appetite, rectal prolapse, salt loss syndrome
Neonates: meconium ileus, prolonged jaundice, failure to pass meconium within 24-48 hours.
Physical Signs:
• Growth parameters: poor weight gain and linear growth despite adequate caloric intake
Respiratory: digital clubbing, hyperinflated chest, adventitious sounds on auscultation
Abdominal: distension, hepatomegaly from fatty infiltration
Salty taste to skin, excessive salt crystals on skin surface.
Severity Assessment:
• Mild CF: minimal respiratory symptoms, pancreatic sufficient (10-15% of patients), normal or near-normal growth
Moderate CF: chronic respiratory symptoms, pancreatic insufficient, some growth impairment, intermittent exacerbations
Severe CF: significant respiratory disease, severe malnutrition, frequent hospitalizations, multi-organ complications.
Differential Diagnosis:
• Primary ciliary dyskinesia (PCD), immunodeficiency disorders, asthma with growth failure, chronic sinusitis, bronchiectasis from other causes, pancreatic insufficiency from other etiologies, celiac disease, inflammatory bowel disease
Sweat test and genetic testing differentiate CF from mimicking conditions.
Diagnostic Approach
History Taking:
• Detailed family history including consanguinity, unexplained infant deaths, chronic respiratory or gastrointestinal symptoms in relatives
Birth history including meconium ileus or delayed passage of meconium
Growth pattern assessment from birth
Recurrent infection history and hospitalization patterns.
Investigations:
• Newborn screening: elevated IRT (>99.9th percentile) prompts genetic analysis or repeat IRT
Sweat chloride test: gold standard with levels ≥60 mEq/L diagnostic, 30-59 mEq/L intermediate, <30 mEq/L normal
Genetic testing: identifies CFTR mutations and guides therapy
Comprehensive CFTR genetic analysis if clinical suspicion high.
Normal Values:
• Normal IRT levels <99th percentile for age (typically <70 ng/mL in first 48 hours)
Normal sweat chloride <30 mEq/L, intermediate 30-59 mEq/L, abnormal ≥60 mEq/L
Adequate sweat collection requires >75 mg (>15 mg in newborns)
Normal pancreatic elastase >200 mcg/g stool indicates pancreatic sufficiency.
Interpretation:
• CF diagnosis requires: clinical features consistent with CF plus elevated sweat chloride ≥60 mEq/L on two occasions, OR clinical features plus two disease-causing CFTR mutations, OR abnormal newborn screen plus clinical features or family history
Intermediate sweat chloride values require further evaluation.
Management/Treatment
Acute Management:
• Pulmonary exacerbations: IV antibiotics based on sputum culture sensitivities (typically 14-day courses), increased airway clearance, nutritional optimization, steroid consideration for severe cases
Meconium ileus: surgical consultation, contrast enemas may be therapeutic, fluid and electrolyte management
Distal intestinal obstruction syndrome: oral contrast, prokinetic agents.
Chronic Management:
• CFTR modulators based on genotype: ivacaftor for gating mutations (G551D, others), lumacaftor/ivacaftor or tezacaftor/ivacaftor for F508del homozygotes, elexacaftor/tezacaftor/ivacaftor for F508del (one or two copies)
Airway clearance: chest physiotherapy, vest therapy, PEP devices
Chronic therapies: hypertonic saline, dornase alfa, chronic antibiotics for P
aeruginosa.
Lifestyle Modifications:
• High-calorie, high-fat diet with 120-150% normal caloric requirements
Pancreatic enzyme replacement with all meals and snacks
Fat-soluble vitamin supplementation (A, D, E, K)
Salt supplementation especially in hot weather
Regular exercise as tolerated
Infection control measures including hand hygiene.
Follow Up:
• Quarterly visits at accredited CF care centers with multidisciplinary team (pulmonologist, nutritionist, social worker, respiratory therapist, pharmacist)
Annual assessments: pulmonary function tests, oral glucose tolerance test, bone densitometry, liver function, vitamin levels
Chronic infection surveillance with quarterly sputum cultures.
Age-Specific Dosing
Medications:
• CFTR modulators: Ivacaftor 75mg BID (2-5 years), 150mg BID (≥6 years)
Elexacaftor/tezacaftor/ivacaftor: not approved <12 years, 2 tablets AM + 1 tablet PM (≥12 years)
Pancreatic enzymes: 1,000-2,500 lipase units/kg/meal, titrated based on symptoms and growth
Hypertonic saline 3-7%: 4mL BID via nebulizer.
Formulations:
• Ivacaftor 75mg, 150mg tablets and oral granules for young children
Elexacaftor/tezacaftor/ivacaftor combination tablets
Pancreatic enzymes: enteric-coated microspheres or mini-tablets in various strengths
Dornase alfa 2.5mg/2.5mL nebulizer vials
Hypertonic saline 3%, 7% nebulizer solutions.
Safety Considerations:
• CFTR modulator monitoring: transaminase elevations (check ALT/AST before treatment, every 3 months first year), drug interactions with CYP3A inhibitors/inducers, cataracts in children
Pancreatic enzyme monitoring: fibrosing colonopathy with excessive dosing (>6,000 units lipase/kg/meal)
Hypertonic saline: bronchospasm risk, pre-bronchodilator recommended.
Monitoring:
• CFTR modulator therapy: liver function tests every 3 months first year then annually, ophthalmologic exams in children, sweat chloride reduction as biomarker
Pancreatic function: fecal elastase annually, symptoms of malabsorption
Growth parameters quarterly, pulmonary function tests quarterly if age-appropriate.
Prevention & Follow-up
Prevention Strategies:
• Primary prevention through genetic counseling for at-risk families, carrier screening programs, and preimplantation genetic diagnosis
Secondary prevention focuses on early detection through universal newborn screening to prevent irreversible complications
Tertiary prevention emphasizes optimal treatment to prevent disease progression and complications.
Vaccination Considerations:
• Standard childhood immunizations plus additional vaccines: annual influenza, pneumococcal vaccines (PCV13 and PPSV23), COVID-19 vaccination as priority population
Live vaccines generally safe unless severely immunocompromised from malnutrition
Household contacts should receive appropriate vaccines including influenza.
Follow Up Schedule:
• Quarterly routine visits at CF care center with interim visits for acute issues
Annual comprehensive assessment including complications screening, nutritional assessment, psychosocial evaluation
Transition planning begins in early adolescence with adult care team introduction
Emergency protocols for pulmonary exacerbations and complications.
Monitoring Parameters:
• Growth velocity using CF-specific growth charts and BMI percentiles
Pulmonary function trends with FEV1 as primary endpoint (when age-appropriate)
Nutritional status: fat-soluble vitamins, essential fatty acids, inflammatory markers
Microbiology surveillance: chronic infection detection and antibiotic resistance patterns.
Complications
Acute Complications:
• Pulmonary exacerbations with increased cough, sputum production, decreased exercise tolerance requiring hospitalization for IV antibiotics
Pneumothorax in 5-10% of adolescents/adults
Distal intestinal obstruction syndrome (meconium ileus equivalent)
Hemoptysis from airway inflammation and infection
Hypoglycemic episodes from CF-related diabetes.
Chronic Complications:
• Chronic respiratory failure requiring lung transplantation evaluation
CF-related diabetes mellitus in 30-50% of adults
Liver disease with portal hypertension in 5-10%
Bone disease and fractures from malabsorption and chronic inflammation
Male infertility (>95%) from congenital bilateral absence of vas deferens.
Warning Signs:
• Respiratory deterioration: increased cough and sputum, fever, decreased exercise tolerance, weight loss, declining pulmonary function
Nutritional concerns: poor weight gain, fat-soluble vitamin deficiencies, signs of diabetes
Gastrointestinal: severe abdominal pain suggesting obstruction, liver-related symptoms.
Emergency Referral:
• Immediate referral for: massive hemoptysis, pneumothorax, severe respiratory distress, distal intestinal obstruction syndrome not responding to medical therapy
Urgent referral for: significant pulmonary function decline, treatment-resistant infections, complications requiring subspecialty management including transplant evaluation.
Parent Education Points
Counseling Points:
• Explain CF as genetic condition requiring lifelong management but with improving outcomes due to better treatments including CFTR modulators
Discuss genetic counseling for family planning with 25% recurrence risk for future pregnancies
Emphasize importance of adherence to treatment regimens for optimal outcomes and quality of life.
Home Care:
• Daily airway clearance techniques appropriate for child's age and preference (vest therapy, manual techniques, exercise)
Proper administration of pancreatic enzymes with all meals and snacks
High-calorie nutritional planning and supplementation
Infection control measures including hand hygiene and avoiding sick contacts.
Medication Administration:
• Pancreatic enzymes must be taken with all meals and snacks, mixed with acidic foods for infants, not chewed
CFTR modulators taken with fat-containing foods to enhance absorption
Nebulized medications in proper sequence (bronchodilator, hypertonic saline, dornase alfa, antibiotics)
Proper nebulizer maintenance and cleaning.
When To Seek Help:
• Contact CF team for: increased cough and sputum production, fever, decreased appetite or weight loss, abdominal pain or constipation, signs of dehydration especially in hot weather
Seek immediate care for: severe breathing difficulty, blood in sputum, severe abdominal pain, signs of pneumothorax (chest pain, sudden breathing difficulty).