Cystic Fibrosis

Aka: Cystic Fibrosis, Mucoviscidosis, Fibrocystic disease of pancreas

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II. Epidemiology

  1. Usually diagnosed in childhood
  2. Carrier rate: 4-5% of Caucasian population
  3. U.S. Prevalence (2024): 40,000
  4. Incidence in live births
    1. Caucasian: 1:1500 to 1:2000 (up to 91% of U.S. CF patients)
    2. Hispanic: 1:9000 (up to 10% of U.S. CF patients)
    3. Black: 1:17000
    4. Asian: 1:90000

III. Pathophysiology

  1. Autosomal Recessive trait (Chromosome 7)
    1. Mutation in CF transmembrane conductance regulator (cftr) Protein
    2. Cftr mutations are grouped into 5 classes, with more than 2000 known mutations
    3. Cftr Protein is a chloride channel on apical membrane of cells (regulates chloride and other molecule flow)
  2. Cftr Protein is present on multiple cell types
    1. Exocrine gland disorder produces mucus blockage
    2. Blocks fine tubules in various organs (respiratory, gastrointestinal, endocrine, Pancreas, reproductive)

IV. History: Presentations

  1. Positive CF Newborn Screening
    1. Universal CF screening in U.S. since 2010
    2. Mild CF or rare mutations may be missed of standard screening (esp. in minority groups)
      1. Missed CF with delayed diagnosis is associated with poor outcomes
  2. Other presentations
    1. Poor weight gain, Failure to Thrive or Malnutrition
    2. Growth Delay
    3. Digital Clubbing
    4. Chronic respiratory symptoms
      1. Cough, Wheezing or Shortness of Breath
      2. Recurrent respiratory or sinus infections
      3. Nasal Polyposis in children
    5. Chronic gastrointestinal symptoms
      1. Steatorrhea or frequent bulky stools

V. Findings

  1. Respiratory
    1. Chronic Cough
      1. Productive of tenacious Sputum
    2. Wheezing
    3. Hemoptysis
    4. Dyspnea
  2. Gastrointestinal
    1. Voracious appetite
    2. Chronic Diarrhea
    3. Bulky malodorous stools
    4. Prolonged Neonatal Jaundice
    5. Unintentional Weight Loss
  3. Other
    1. Excessive sweating
    2. Positive Family History
    3. Digital Clubbing

VI. Complications

  1. Respiratory
    1. Recurrent Pneumonia
    2. Chronic Bronchitis
    3. Recurrent Sinusitis and pansinusitis
    4. Nasal Polyps
    5. Bronchiectasis
    6. Pseudomonas colonization of respiratory tract
    7. Pneumothorax
    8. Respiratory Failure
  2. Gastrointestinal
    1. Meconium ileus
    2. Fecal Impaction
    3. Intussusception
    4. Volvulus
    5. Distal Intestinal Obstruction Syndrome (DIOS, Meconium Ileus Equivalent)
      1. Small Bowel Obstruction in the ileocecal region
      2. Incidence: Occurs in up to 10 to 22% of Cystic Fibrosis patients
      3. Triggered by pancreatic insufficiency, dysmotility and Dehydration
      4. Presents with Right lower quadrant mass
      5. XRay demonstrates obstructive findings, but CT Abdomen is typically required
    6. Failure to Thrive
    7. Rectal Prolapse
    8. Liver disease
  3. Other
    1. Cardiomegaly
    2. Diabetes Mellitus (30% of adults with CF)
    3. Metabolic abnormalities
      1. Hyponatremic Dehydration
      2. Chronic Metabolic Alkalosis
    4. Infertility in males (azoospermia)
    5. Immune mediated joint disease (12%)
      1. Acute Oligoarthritis episodes (asymmetric, lasting 7 to 10 days)

VII. Labs

  1. Sweat Test
  2. Delta F508
  3. Agar Plate hand test
    1. White palmar implant from Sweat Chloride
  4. Starch tolerance test
    1. Pancreatic Insufficiency
  5. Electrolytes
    1. Sodium and chloride normal

VIII. Imaging

  1. Chest XRay
    1. Peribronchial cuffing
    2. Tram lines (Bronchial shadow lines)
    3. Fibrosis
    4. Recurrent infiltrates
    5. Pulmonary Blebs and bullae
  2. Abdominal XRay (KUB)
    1. Dilated loops of Small Bowel

IX. Diagnosis

  1. Newborn Screening positive for 2 CF mutations
    1. Contact local Cystic Fibrosis center
    2. Discuss with family and perform evaluation
    3. Obtain confirmatory diagnostic Sweat Test
  2. Newborn Screening positive for 1 CF mutation
    1. Alternatives: Ultra-high immunoreactive trypsinogen or other presentation as above
    2. Obtain Sweat Chloride test at CFF accredited lab
      1. Sweat Chloride >= 60 mmol/L: Consistent with Cystic Fibrosis (refer as if 2 CF mutations)
      2. Sweat Chloride <= 29 mmol/L: Cystic Fibrosis is unlikely
      3. Sweat Chloride 30 to 59 mmol/L: Intermediate for CF
        1. Consult with local CF center
        2. Consider repeat Sweat Chloride, Genetic Testing or evaluation at CF center

X. Management: General

  1. See Cystic Fibrosis in Pregnancy
  2. Cystic Fibrosis Care Center visits every 3 months
  3. Ongoing monitoring
    1. Annual labs including Liver Function Tests, Glucose (e.g. OGTT, Hemoglobin A1C)
    2. Following care plan (e.g. airway management, supplements, CFTR Modulators)
    3. Annual Vaccinations (e.g. Influenza Vaccine, covid19 Vaccine) as well as Pneumococcal Vaccine
    4. General preventive care and screening (mental health, substance use including Alcohol Use Disorder)

XI. Management: CF Transmembrane Conductance Regulator (CFTR) Modulators

  1. Mechanism
    1. CF disease modifying agents
    2. Partially returns function of chloride channels, resulting in less mucus accumulation
  2. Preparations
    1. Trikafta (elexacaftor/tezacaftor/ivacaftor)
      1. Released in 2020, targets gene mutation found in 90% of CF patients (contrast with 50% for other agents)
    2. Kalydeco
    3. Orkambi
    4. Symdeko
  3. Dosing
    1. To maximize absorption, take with fat containing food such as peanut butter or avocado
    2. Also take with Pancreatic Enzymes (if already taking)
  4. Adverse Effects
    1. Expensive ($300,000 per year)
    2. Liver Function Test Abnormalities
  5. Drug Interactions
    1. Strong CYP3A4 Inducers
    2. Moderate to Strong CYP3A4 Inhibitors
  6. References
    1. (2020) presc lett 27(2):11

XII. Management: Airway management

  1. Airway clearance
    1. Percussion and postural drainage
    2. Active cycle breathing
    3. Positive expiratory pressure mask
    4. Autogenic drainage
    5. Flutter valve
    6. Pneumatic vest
  2. Mucus thinning drugs
    1. Pulmozyme 2.5 mg nebulized qd
    2. Efficacy maintained for up to 1 year of treatment
    3. Reduces rate of respiratory infection
    4. Improves pulmonary function
  3. Antibiotics: Nebulized Tobramycin
    1. Traditional Tobramycin
      1. Dose: 80 mg/2cc nebulized TID
    2. TOBI
      1. Dose: 300 mg/5cc nebulized bid via Pari LC Plus
      2. Cost: $2000/28 day supply
  4. Antibiotics: Pneumonia
    1. Under age 10 years: Multiple organisms
    2. Age 10 and older: Pseudomonas predominates

XIII. Management: Nutritional Supplements and Gastrointestinal Symptoms

  1. Background
    1. Nutritional status impacts longterm survival and pulmonary function
  2. Targets
    1. Dietary plan maintains 90% of Ideal Body Weight (or BMI 22 to 25 kg/m2)
  3. Labs
    1. Monitor pancreatic exoocrine function (with fecal pancreatic elastase)
  4. Supplements as needed
    1. Daytime
      1. Scandibar 350 cals/bar
      2. Scandishake 600 cals/8 oz (with WCM)
      3. Calories Plus 450 cals/8 oz (with water)
      4. Carnation Instant Breakfast 290 Cals/8 oz
    2. Nighttime drip (e.g. Gastrostomy Tube)
      1. Tolerex 1.0 cal/cc
      2. Vital 1.0 cal/cc
      3. Peptamen 1.0 cal/cc
      4. Criticare 1.0 cal/cc
  5. Other gastrointestinal symptoms
    1. Gastroesophageal Reflux management
      1. Proton Pump Inhibitors or H2 Blockers
    2. Constipation (common)
      1. See Chronic Constipation

XIV. Management: Other

  1. Growth Hormone
    1. Improved Growth Velocity improves pulmonary function
    2. Results in reduced hospitalization rates
    3. Hardin (2006) J Clin Endocrinol Metab 91:4925-9 [PubMed]
  2. Lung Transplantation
    1. See Lung Transplantation in Cystic Fibrosis
  3. Advanced Directives
    1. Discuss end of life issues as part of routine Health Maintenance

XV. Management: Hospitalization Indications

  1. Increased cough
  2. Increased Sputum production or color change
  3. Anorexia and weight loss
  4. Exercise intolerance
  5. Malaise or irritability
  6. Decline in pulmonary function or CXR change

XVI. Prognosis

  1. Mean survival has significantly improved from age 36 years (2006) to age 53 years (2021)

XVII. References

  1. Fuchs and Yamamoto (2011) APLS, Jones and Bartlett, Burlington, p.76-9
  2. Acherman (1998) PREP Course, Phoenix
  3. Collins (2024) Am Fam Physician 109(5): 388-90 [PubMed]
  4. Wallace (1993) Clin Pharm 12:657-74 [PubMed]

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Related Studies

Ontology: Cystic Fibrosis (C0010674)

Definition (MEDLINEPLUS)

Cystic fibrosis (CF) is an inherited disease of the mucus and sweat glands. It affects mostly your lungs, pancreas, liver, intestines, sinuses and sex organs. CF causes your mucus to be thick and sticky. The mucus clogs the lungs, causing breathing problems and making it easy for bacteria to grow. This can lead to problems such as repeated lung infections and lung damage.

The symptoms and severity of CF vary widely. Some people have serious problems from birth. Others have a milder version of the disease that doesn't show up until they are teens or young adults.

Although there is no cure for CF, treatments have improved greatly in recent years. Until the 1980s, most deaths from CF occurred in children and teenagers. Today, with improved treatments, some people who have CF are living into their forties, fifties, or older.

NIH: National Heart, Lung, and Blood Institute
Definition (MSHCZE) Zkr. CF, mukoviscidóza – autozomálně recesivně dědičné, relativně časté onemocnění žláz se zevní sekrecí. Problémem je defektní transport iontů zvyšující viskozitu sekretů exokrinních žláz. Mutován je gen pro CFTR na 7. chromozomu. Nápadná je vysoká koncentrace chloridů v potu (lze využít i diagnosticky, tzv. potní test). Porucha jejich funkce se projevuje zejm. v plicích (opakované záněty při ucpávání průdušek hleny, porucha dýchání, respirační insuficience), v trávicím ústrojí (porucha trávení při nedostatečnosti slinivky břišní). Bývá sterilita či snížená fertilita, vyšší je rovněž výskyt diabetu (srov. CFRD). Navazují i příznaky podmíněné malabsorpcí. Některé z těchto příznaků vystupují do popředí s prodlužujícím se životem postižených. V terapii jsou důležitá antibiotika, péče o drenáž dýchacích cest, symptomatická terapie trávicích obtíží, péče o výživu, ev. protizánětlivé léky; z moderních postupů transplantace plic a v budoucnosti genová terapie. Projevuje se od raného dětství, dř. se děti nedožily puberty, v dnešní době se s intenzivní terapií většina dožívá dospělosti. (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ )
Definition (NCI_NCI-GLOSS) A common hereditary disease in which exocrine (secretory) glands produce abnormally thick mucus. This mucus can cause problems in digestion, breathing, and body cooling.
Definition (NCI) A congenital metabolic disorder affecting the exocrine glands, inherited as an autosomal trait. The secretions of exocrine glands are abnormal, resulting in excessively viscid mucus production which causes obstruction of passageways (including pancreatic and bile ducts, intestines, and bronchi). The sweat sodium and chloride content are increased. Symptoms usually appear in childhood and include meconium ileus, poor growth despite good appetite, malabsorption and foul bulky stools, chronic bronchitis with cough, recurrent pneumonia, bronchiectasis, emphysema, clubbing of the fingers, and salt depletion in hot weather.
Definition (MSH) An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.
Definition (CSP) most common potentially lethal autosomal recessive disease affecting Caucasians; characterized by chronic pulmonary, intestinal, liver, pancreatic, and exocrine gland dysfunction; caused by mutations of the CFTR chloride channel.
Concepts Disease or Syndrome (T047)
MSH D003550
ICD9 277.0
ICD10 E84 , E84.9
SnomedCT 85809002, 190911006, 154767009, 190905008
LNC LP56779-9, MTHU021607, LA12537-9
English Cystic Fibrosis, Mucoviscidosis, Fibrosis, Cystic, Cystic fibrosis NOS, Cystic fibrosis, unspecified, CYSTIC FIBROSIS, MUCOVISCIDOSIS, cystic fibrosis, cystic fibrosis (diagnosis), CF (cystic fibrosis), Cystic Fibrosis [Disease/Finding], cystic disorder fibrosis, Disease;fibrocystic, cystic fibrosis (CF), diseases fibrocystic, fibrocystic disease of pancreas, disease fibrocystic, cystic fibrosis pancreas, disease fibrocystic pancreas, pancreas cystic fibrosis, Cystic fibrosis NOS (disorder), Fibrocystic disease, Cystic fibrosis, CF, CF - Cystic fibrosis, Cystic fibrosis (disorder), mucoviscidosis, cystic; fibrosis, disease; fibrocystic, fibrocystic; disease, fibrosis; cystic, Cystic fibrosis (disorder) [Ambiguous], fibrocystic disease
French MUCOVISCIDOSE, Fibrose kystique, Mucoviscidose SAI, Mucoviscidose
Portuguese MUCOVISCIDOSE, Fibrose quística NE, Fibrose cística, Fibrose Cística, Mucoviscidose
Spanish MUCOVISCIDOSIS, Fibrosis quística NEOM, fibrosis quística, SAI, fibrosis quística, SAI (trastorno), mucoviscidosis, SAI, FQ, enfermedad fibroquística, fibrosis quística (concepto no activo), fibrosis quística (trastorno), fibrosis quística, mucoviscidosis, Fibrosis quística, Mucoviscidosis, Fibrosis Quística
Dutch cystische fibrose NAO, mucoviscidose, cystisch; fibrose, fibrocysteus; ziekte, fibrose; cystisch, ziekte; fibrocysteus, Cystische fibrose, niet gespecificeerd, cystische fibrose, Cystische fibrose, Fibrose, cystische, Mucoviscidose, Taaislijmziekte
German zystische Fibrose NNB, MUKOVISZIDOSE, Zystische Fibrose, nicht naeher bezeichnet, zystische Fibrose, Mucoviscidosis, Mukoviszidose, Pankreasfibrose, zystische, Zystische Fibrose, Zystische Pankreasfibrose
Italian Fibrosi cistica NAS, Mucoviscidosi, Fibrosi cistica
Japanese 嚢胞性線維症ＮＯＳ, ﾉｳﾎｳｾｲｾﾝｲｼｮｳNOS, ﾉｳﾎｳｾｲｾﾝｲｼｮｳ, 膵線維症, 嚢胞性線維症, ｽｲｾﾝｲｼｮｳ, のう胞性線維症, のう胞性膵線維症, ムコビシドーシス, 嚢胞性膵線維症, 線維性嚢胞膵症, 膵のう胞性線維症, 膵嚢胞性線維症, 膵臓線維症
Swedish Cystisk fibros
Czech mukoviscidóza, cystická fibróza, Mukoviscidóza, Cystická fibróza, Cystická fibróza NOS
Finnish Kystinen fibroosi
Russian PANKREATICHESKII KISTOZNYI FIBROZ, PANKREOFIBROZ, KISTOZNYI FIBROZ, MUKOVISTSIDOZ, FIBROZNO-KISTOZNAIA BOLEZN' PODZHELUDOCHNOI ZHELEZY, КИСТОЗНЫЙ ФИБРОЗ, МУКОВИСЦИДОЗ, ПАНКРЕАТИЧЕСКИЙ КИСТОЗНЫЙ ФИБРОЗ, ПАНКРЕОФИБРОЗ, ФИБРОЗНО-КИСТОЗНАЯ БОЛЕЗНЬ ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ
Korean 상세불명의 낭성 섬유증, 낭성 섬유증
Croatian CISTIČNA FIBROZA
Polish Torbielowate zwłóknienie trzustki, Choroba włóknisto-torbielowa trzustki, Mukowiscydoza
Hungarian ((clarke-hadefield syndroma)), Cystikus fibrosis k.m.n., Cystikus fibrosis
Norwegian Cystisk fibrose, Mukoviskidose, Mucoviscidosis
Derived from the NIH UMLS (Unified Medical Language System)

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