Cystic Fibrosis

nutritional status and CF

poor nutritional status linked to accelerated lung disease and death

pharmacuticals for treatment/maintenance CF

flu vaxx all pt over 6 y/o palivizumab prophy for RSV under 2 y/o H.flu vaxx pneumococcal vaxx avoidance of drugs Orkambi over 12 y/o Kalydeco *ivacaftor* over 2 y/o for class III

treatment for mild exacerbation pneumonia in CF

PO Bactrim or Cephalexin (S. aureus) *likely child* PO Ciprofloxacin (P. aeruginosa) *likely adults*

Cystic Fibrosis eitology

*Autosomal recessive* inheritance mutation of Cystic Fibrosis Transmembrane Conductance regulator gene (CFTR gene) >2000 CFTR mutations

criteria for diagnosis of CF

*CFTR genes/IRT*(*immunoreactive trypsinogen*) *blood test* (*precursor of pancreatic*trypsin enzyme) *if positive Confirm with Sweat Test* (aka: Sweat chloride; Iontophoretic sweat test) This test is the most useful test for diagnosing CF. *NaCl gets reabsorbed in sweat glands, CF patients will have Cl left behind in sweat*

Progressive lower respiratory track symptoms

*Cough* that becomes *persistent* *Persistent wheezing* *Excessive sputum* production *Barrel chest* —occurs w/ late (advanced) disease *Recurrent/severe pneumonia* *Digital clubbing*— Bulbous swelling of finger tips Chronic hypoxia (?)—later in disease

Problems with having thick, sticky, mucus secretions with CF

*Decreased mucocillary* movement and clearance *Depletion of airway* surface liquid and *dehydration of mucous* *Adherence of mucous to epithelium* forming *bacterial biofilm* that leads to *infection* and *plugging* *Presence of neutrophilic DNA* (from autolysis of neutrophils) increases mucous viscosity *Mucus secretions lead to degradation of supporting tissues* causes bronchiectasis and eventual failure.

Bronchiectasis etiology

*Direct damage*: Pneumonia, TB, Fungal *infections* *Diseases*: CF, chronic aspiration, AIDS, *Airway blockage*: cancer, foreign body

prophy treatment for pneumonia with CF patients

*Long term antibiotics* *Azithromycin* (has anti-inflammatory properties, not sure about its antibacterial actions in this setting) *Inhaled Tobramycin* *for* *pseudomonas coverage*

non-pulmonary symptoms

*Meconium Ileus* Earliest clinical presentation (infants)(10-20%) *Pancreatic insufficiency* *(85-90%)* Pancreatic *enzymes trapped in ducts* Causes *pancreatic autolysis* Malabsorption and malnutrition Diabetes *Constitutional symptoms* Low grade fever, weight loss *Failure to thrive a hallmark of CF in children* is poor weight gain and growth. *Due to malabsorption*

mechanism leading to respiratory failure/death with CF

*Mucous plugging* *Chronic inflammation* *Infection* Pneumonia *Bronchiectasis*, focused then widespread *Parenchymal involvement* later stages Microabscesses Consolidation Fibrosis *Cor Pulmonale* (*right side heart failure*) Pulmonary hypertension

A pediatric patient presents with a history of multiple recurrent respiratory infections associated with failure to thrive. A sweat chloride test is elevated. What is the common cause of death in patients with this condition?

*Pulmonary infection* The most common causes of death include pulmonary complications, such as infections, and terminal chronic respiratory failure associated with cor pulmonale.

lung transplant with CF

*definitive treatment* only 3 years survival rate is 55% due to use of immunosupressive drugs some lobar transplantations is offered

Cystic fibrosis pathophysiology

*genetic mutation of CFTR protein which regulates Cl and Na* across cell membranes *Cl can not leave, creating thick sticky mucous* respiratory failure is main cause of death *95% die from lung infection complication* poor nutritional status

GI treatment for CF

*pancreatic enzymes* fat-soluble vit supplements *A,D,E,and K* treat liver disease *UDCA*

bacteria which colonizes in lungs of CF patients

*pseudomonas aeruginosa after 24 y/o* *75%* of patients with CF adheres to mucoid biofilms *highly resistant to Abx and immune* (goal is to suppress infection) *staph aureus and H.Flu* children (*goal is delaying P.aeruginosa infection*) *Burkholderia cepacia* complex Not as common but *most deadly* (need ID consult)

cystic fibrosis upper respiratory track symptoms

*recurrent with periods of stability and exacerbations* chronic sinusitis *very common* Nasal polyps

Cystic fibrosis lower respiratory track symptoms

*recurrent with periods of stability and exacerbations* persistent, purulent productive cough dyspnea with hypoxia

pulmonary function test CF

*starts as Obstructive pattern* in CF progressing to *restrictive pathology in later disease* Increased disease progression with age: *Decreased FEV1, FVC (forced vital capacity), and TLC* Some Pts have near *normal* PFTs for *many yrs then rapidly decline*

median age of diagnosis for CF

6-8 months

key points CF

CF occurs in 1/3500 Caucasian births All newborns should be screened using the new algorithms with sweat chloride testing The median survival has increased to 40 y/o in the U.S. CF with persistent P.aeruginosa cultures should have inhaled tobramycin prophylactically New approved medications (Ivacaftor) recommended for Class III mutations

differential diagnosis GI with cystic fibrosis

Celiac disease Protein-losing enteropathy Pancreatitis of unknown etiology

treatment and maintenace CF

Chest physiotherapy exercise *mobilize secretions/increase FEV* positive expiratiory pressure mask *improves expiration/secretion* inhaled DNAse *decrease viscosity* inhaled hypertonic saline *increase clearance*

Class of CF which drug treatment is successful

Class III *only 4% of cases are this class* defective channel regulation CFTR reaches cell surface but does not properly open Cl transport

differential diagnosis pulmonary CF

Difficult-to-manage asthma Chronic bronchitis Recurrent pneumonia Chronic/recurrent sinusitis Primary ciliary dyskinesia

infancy presentation CF

Failure to thrive Chronic diarrhea

CXR with CF patients

Hyperinflation seen in early disease process Hilar adenopathy Interstitial Infiltrates Atelectasis Bronchiectasis Diffuse fibrosis

neonatal presentation CF

Meconium ileus Prolonged jaundice

GI presentations cystic fibrosis

Meconium ileus Abdominal distention Intestinal obstruction Increased frequency of stools Failure to thrive (despite adequate appetite) Flatulence or foul-smelling flatus, steatorrhea Recurrent abdominal pain Jaundice GI bleeding

symptoms which are present in infants and children prior to screening

Meconium ileus - 10-20% of patients *baby can't pass first stool* Respiratory symptoms - 45% of patients Failure to thrive - 28% of patients

complications of colonized lung CF patients

Microabscesses increased inflammatory response bronchiectasis hemorrhagic pneumonia

childhood presentation CF

Recurrent endobronchial infection Bronchiectasis Recurrent sinusitis Steatorrhea Poor growth DIOS(Distal Intestinal Obstruction Syndrome)

adolescence and adulthood presentation CF

Recurrent endobronchial infection Bronchiectasis Chronic sinusitis/Hemoptysis Pancreatitis Delayed puberty

treatment for severe exacerbation pneumonia in CF

Require IV antibiotics Hospitalization *Zosyn* (piperacillin and tazobactam) or *nafacillin* (*S. aureus*) *Vancomycin or Linezolid* (*MRSA*) *Zosyn, ceftazadime plus tobramycin* (*two classes P. aeruginosa*) Burholderia cepacia (as per individual—need ID consult—≥3 ABXs)

genitourinary (GU) presentation cystic fibrosis

Undescended testicles or hydrocele Delayed secondary sexual development Amenorrhea *99% of males are infertile*

ongoing care for CF patients

after pulmonary exacerbation follow up 2-4 weeks routine visit Q3months annual nutrition eval glucose test (OGTT) after 10 y/o bone density after 18 y/o high cal diet with added salt

progressive parenchymal complications with CF

cysts bullae hemoptysis hemorrhagic pneumonia pulmonary hypertension cor pulmonale (RHF) *from pulmonary HTN*

Bronchiectasis

damage to the bronchi /bronchioles causes them to widen and become flabby and scarred

bronchiectasis pathology

inability to clear out mucus leads to repeated, serious lung infections. Each infection causes more damage. Causing respiratory failure, atelectasis , and heart failure.

bronchiectasis presentation

signs and symptoms *may not appear until months or even years* after having repeated lung infections A *daily cough* that occurs over months or years Daily production of *large amounts of sputum* SOB and wheezing Chest pain Clubbing