Bronchiectasis & Cystic Fibrosis Flashcards
bronchiectasis - overview & clinical definition
*IRREVERSIBLE DILATION OF THE AIRWAY
*commonly associated with the medium-large airways
*mucous commonly present
*can be focal or diffuse disease
*most easily diagnosed on CT of the chest, but can be seen on CXR
non-CF bronchiectasis - clinical manifestations
*anatomic distortion of airways results in recurrent infections that manifest as:
-CHRONIC COUGH (productive or non-productive)
-dyspnea
-wheezing
-HEMOPTYSIS
-nonspecific symptoms (fatigue or weight loss)
-found in all ages, women > men
etiologies of bronchiectasis
- post-infectious: TUBERCULOSIS (most common cause), other infections
- anatomic disease
- immune-related diseases
- immune deficiencies
- GENETIC (CYSTIC FIBROSIS, primary ciliary dyskinesia, alpha-1 antitrypsin deficiency)
- idiopathic
most common causes of bronchiectasis
*TUBERCULOSIS is the #1 cause
*genetic abnormalities are another important cause:
1. cystic fibrosis
2. primary ciliary dyskinesia
3. alpha1 antitrypsin deficiency
primary ciliary dyskinesia (PCD) - inheritance pattern & genes involved
*AUTOSOMAL RECESSIVE disorder
*most common genes involved: DNAI1 and DNAH5
*50% have situs inversus totalis [all of the organs are inverted]- due to role of cilia in fetal development
genes involves in primary ciliary dyskinesia
*DNAI1 and DNAH5
non-CF bronchiectasis - diagnosis
*symptoms are non-specific
*diagnosis relies on radiographic images
*CXR: “tram tracks” and peribronchial cuffing (bronchial wall thickening)
*CT SCAN: defined by either…
1. lack of bronchial tapering (visibility of peripheral airways)
2. bronchial dilation to a diameter greater than that of the accompanying artery = “SIGNET RING”
Signet Ring on CT of chest is indicative of…
bronchiectasis
note - signet ring means bronchial dilation to a diameter greater than that of the accompanying artery
bronchiectasis - genetic workup
*CF testing
*A1AT level and genotype
*PCD genetic testing
bronchiectasis treatment
- airway clearance (clearing airways of mucous plugs = AUGMNETED AIRWAY CLEARANCE TECHNIQUES):
-flutter valves, high-frequency chest oscillation, etc
-bronchodilators - prevention (vaccines)
- antibiotics for exacerbations (acute infections)
bronchiectasis - complications
*HEMOPTYSIS (coughing up blood) - can be life threatening
*empyema
*lung abscess
*Cor pulmonale
cystic fibrosis - inheritance pattern & genes involved
*AUTOSOMAL RECESSIVE
*results from a dysfunction CF Transmembrane Conductance Regulator (CFTR)
*encoded by CFTR gene on Chromosome 7
cystic fibrosis pedigree: if both parents are carriers…
*25% chance of normal genetics
*50% chance of carrier status
*25% chance of disease
cystic fibrosis pedigree: if 1 normal parent and 1 carrier parent
*50% chance of normal genetics
*50% chance of carrier status
cystic fibrosis pedigree: carrier parent with a CF parent
*50% chance of carrier
*50% chance of disease
function of CF transmembrane conductance regulator (CFTR) - general
*CFTR functions as a CHLORIDE CHANNEL
*inhibits sodium transport through the epithelial sodium channels in airways
*expressed in various tissues, including:
-LUNGS
-SWEAT GLANDS
-pancreas
-liver
normal function of CFTR in SWEAT GLANDS
*CFTR present on the membrane of the sweat duct, facing the lumen
*when we sweat, CFTR is REABSORBING CHLORIDE into the cell; sodium follows; results in hypotonic sweat
normal function of CFTR in LUNGS
*CFTR moves chloride (Cl-) from the cells INTO THE AIRWAYS; sodium follows, as does water
*this is good, because fluid helps keep the secretions loose
function of CFTR in the SWEAT GLANDS in CF patients
*CFTR is not present, so we cannot reabsorb the Cl- from sweat
*therefore, sodium also stays in the sweat
*results in hypertonic sweat (excess chloride and sodium in the sweat because we are not reabsorbing it)
function of CFTR in the LUNGS in CF patients
*CFTR is NOT moving chloride INTO the airway, so sodium and water remain in the cells, rather than the airway
*results in dry, dehydrated mucous, which is difficult to clear and plugs the airways
cystic fibrosis: diagnostic testing
*newborn screening: immunoreactive Trypsinogen
*sweat chloride testing:
-induce sweating and measure amount of chloride
-elevated sweat chloride is considered diagnostic
*GENETIC TESTING:
1. genotyping
2. full sequencing to look for genetic variants
homozygous deltaF508 (class II) cystic fibrosis
*most common mutation found in cystic fibrosis
*deltaF508: missing phenylalanine (F) at position 508
*misfolded CFTR protein → retained in rough ER and doesn’t reach the cell membrane (trafficked to proteasome) → inhibits chloride transport
*causes hyperviscous secretions, blocks ducts and airways leading to damage of organs
cystic fibrosis - clinical presentation
*CF is a systemic disease and affects multiple organ systems:
-respiratory symptoms (bronchiectasis, recurrent infections, respiratory failure)
-GI symptoms (meconium ileus)
-pancreatic issues
-failure to thrive/malnutrition
-infertility (esp. in men)
cystic fibrosis - treatments
*airway clearing techniques
*CFTR modulators
*thinning secretions (mucolytics, hypertonic saline)
*bronchodilators
*anti-inflammatories (azithromycin)
cystic fibrosis: antimicrobial therapy
*CF-related bronchiectasis is a cycle of INFECTION, inflammation, and impaired mucociliary clearance
*most common pathogens:
-peds = S. aureus
-adults = PSEUDOMONAS
*PSEUDOMONAS contributes greatly to morbidity/mortality
cystic fibrosis - signs and symptoms of an exacerbation of pulmonary infection
*increased frequency and duration of cough
*increase in sputum volume
*HEMOPTYSIS
*fever or leukocytosis
*weight loss
*increased respiratory rate
*CHANGE IN SPIROMETRY (decrease in FEV1 from baseline)
CFTR modulators
- protein potentiation - improve chloride transport efficiency (ex. Ivacaftor)
- protein stabilization - improve protein delivery to cell surface (ex. lumacaftor, tezacaftor, etc)
cystic fibrosis - complications
*hemoptysis (can be life-threatening)
*allergic bronchopulmonary aspergillosis (ABPA)
*pneumothorax
*Cor pulmonale
