Cystic Fibrosis, Bronchiectasis and Bronchiolitis

Bronchiolitis (General)

PP: inflammation/narrowing/obliteration of bronchioles

RF: toxic fumes
viral infxns
organ transplant
CTD

CM: insidious onset cough
dyspnea

DX: spirometry→irreversible airflow obstruction
CXR→none

Constrictive Bronchiolitis/Obliterative Bronchiolitis/Bronchiolitis Obliterans

PP: inhalation of toxins/autoimmune response→inflammation of sub-epithelial structures+dysregulated repair→fibroproliferation+abnormal regeneration of epithelium of small airways

hypertrophy
-smooth muscles
-bronchioles
-peribronchial inflammatory infiltrates
-mucus accumulation
-scarring

E: uncommon
inhalation injury
-toxins
-dusts
-ammonia
-vaping

postinfectious rxns
RA
SLE
mx

non infectious
-lung transplant
-stem cell transplant
-IgE autoimmune response

CM: dyspnea
persistent+progressive cough
wheezing
-x wks-months
-persistent+progressive

PE: decreased breath sounds
prolonged expiratory phase
rales/crackles

DX:
spirometry
-obstructive airway dx
-unresponsive to bronchodilators

CXR→hyperinflation

chest CT
-air trapping
-bronchial wall thickened
-scattered ground glass opacities

DX fail→lung biopsy

TX: azithromycin

progressive+deteriorating→no steroids

triple therapy
-fluticasone
-montelukast
-azithromycin

post lung transplant→augment immunosuppression
add ins:
-tacrolimus
-cyclosporine
-mycophenolate mofetil
-prednisone

Bronchietasis

PP: congenital/acquired disorder of large bronchi→permanent+abnormal dilation+destruction of bronchial walls
-full PP→look at other slide

E: CF (50%)
lung infxn
abnormal host defense mechanisms
localized airway obstruction
immunodeficiency
-tumors
-foreign body
-mucoid impaction
host defense mechanism impairment

CM: chronic productive cough (cough+sputum) x months-years
hemoptysis
pleuritic chest pain
dyspnea
wheezing
weight loss

PE: anemia
crackles
finger clubbing

DX: spirometry→obstructive airway dx
O2→hypoxemia

1st line→chest HRCT

• bronchoarterial ratio 1.0+

• lack of bronchial tapering

• “tram tracks”

CXR
-dilated+thickened bronchi (“tram tracks”)
-scattered+irregular opacities
-atelectasis (collapse of lung tissue)
-focal consolidation (lung tumor)

sputum culture

• h influenzae

• p aeruginosa

• s pneumoniae

• s aureus

TX:
NP: chest PT x daily
postural drainage
chest percussion
inhaled bronchodilators
retained secretions removal→bronchoscopy

MX: amoxicillin q8h
augmentin q8h
ampicillin 16h
doxycycline BID
bactrim DS BID
ciprofloxacin BID

prophx (copious+purulent sputum)
-azithromycin TIW x 6 months
-azithromycin daily x 12 months

C: pneumonia
empyema
respiratory failure
hemoptysis→bronchoscopy+embolization/surgical resection
cor pulmonale
amyloidosis
distant sites→secondary visceral abscesses

P: good
varies with underlying cause
CF→worse prognosis
tx compliance→good

Cystic Fibrosis (CF)

PP: CFTR (CF transmembrane conductance regulator) gene mutation→multisystem disorder+elevated sweat chloride levels (60+ mmol/L)
-respiratory
-pancreatic
-GI
-male reproductive system
-full PP→on other slide

RF: chronic lung dx
pancreatitis
infertility

E: young adult
white
35,000 in USA

CM: cough
dyspnea
sputum production
decreased exercise tolerance
hemoptysis
chronic rhinosinusitis
diarrhea
steatorrhea
abdominal pain
low BMI
decreased growth
men→congenital BL vas deferens absence+azoospermia
etc.

DX: spirometry→mixed+obstructive+restrictive pattern

CXR/chest CT
early hyperinflation
peribronchial cuffing
mucus plugging
bronchiectasis

pilocarpine sweat test (peds)→elevated sweat chloride levels (over 60 mEq/L)
+→DNA analysis

CFTR genotyping

Pilocarpine Sweat Test

for CF in infants→CF confirmation

most important DX test

+: defective chloride channels→elevated sweat concentration→elevated Na+Cl levels (over 60+ mEq/L)

dx: 2 test on different days

normal results→gene testing/other dx

Cystic Fibrosis Diagnostic Criteria

at least one of list 1+ at least one of list 2

list 1

• COPD

• chronic sinusitis

• GI+nutrition abnormalities

• salt loss syndromes

• obstructive azoospermia

• sibling FHx

• positive newborn screening test

list 2

• elevated sweat chloride concentration

• 2 CFTR gene mutations on separate alleles

• NPD testing abnormalities

Cystic Fibrosis Tx

NP:

conventional (1st line)
clear+reduce lower airway secretions
bronchioconstriction reversal
tx respiratory tract infxn+bx burden
pancreatic enzyme replacement
nutrition+psych support
CF center referral

lower respiratory
postural drainage
chest percussion
chest vibration
positive expiratory pressure (PEP)
flutter valve breathing device
directed cough

full tx
-heart-lung transplant
-double lung transplant

MX:
gene mutation→CFTR modulators→HEMT

• elexacaftor-tezataftor-ivacaftor

• ivacaftor

• vanzacaftor-texacaftor-deutivacaftor

inhaled recombinant human DNA
hypertonic saline nebulizer BID

sputum infxn→abx
-azithromycin qTIW
-tobramycin B/TID
-aztreonam
-levofloxacin

12+% FEV1 increase→inhaled bronchodilator

persistent asthma/allergic pulmonary mycosis→inhaled corticosteroid

Cystic Fibrosis C+P

C: nasal polyps
chronic sinusitis
vitamin deficiency
osteoporosis
bronchiectasis
atelectasis
pneumothorax
hemoptysis
pulm HTN
cor pulmonale
chronic respiratory failure
etc.

P: post transplant median survival→7.8 years
medial survival age→39+ y/o
pulm complications→death
chronic respiratory failure→death
cor pulmonale→death

Proliferative Bronchiolitis

PP/E: infxn
aspiration
ARDS
hypersensitivity pneumonitis
CTD
organ transplant

organizing PNA
inflammatory cells extend into distal lung parenchyma

CM:
masson bodies

• intraluminal fibrotic buds

• extend to the alveoli+exudate

TX:
initiation→prednisone x 1-3 months→taper x 3-6 months

Follicular Bronchiolitis

PP: lymphoid hyperplasia of bronchus-associated lymphoid tissue (BALT)

E: connective tissue dx (CTD)
HIV
hypersensitivity pneumonitis

DX:
chest HRCT

• centrilobular+peribronchial nodules

• tree-in-bud pattern

• ground-glass pattern

Respiratory Bronchiolitis

PP: pigmented macrophages accumulate in respiratory bronchioles+adjacent alveoli→peribronchiolar inflammation

RF→cigarette smoking

DX:
PFR→mixed obstructive-restrictive pattern
CXR→nodular/reticular opacities
unclear→lung biopsy

HRCT

• poorly-defined certilobular nodules

• patchy ground-glass opacities

• bronchial wall thickening

• occasional air trapping

TX: smoking cessation
avoid second-hand smoke exposure
steroids (limited benefit)

Diffuse Panbrochiolitis

RF: china
korea
japan
men
hx of chronic sinusitis x yrs-decased before sxs

CM: productive cough
dyspnea
chronic pansinusitis
crackles
rhonchi

DX:
spirometry→obstructive airway dx
CXR→diffuse+small+nodular shadows with hyperinflation

TX→azithromycin

Bronchiectasis Pathophysiology (Full)

acquired weakening/destruction of muscular+elastic parts of bronchial walls→permanent abnormal dilation of bronchi→destruction of bronchial walls

persistent microbial infxn+postobstructive pneumonia→distal lung parenchyma affected→abnormal mucous clearance→mucus stasis→bacteria colonization→neutrophil release→persistent infection+inflammation

Cystic Fibrosis (CF) Pathophysiology (Full)

mutations of CF transmembrane conductance regulator (CFTR) gene→altered chloride transport+water reflux across apical surface of epithelial cells→deranged transport of chloride+CFTR affected ions→thick+viscous secretions→obstruction of glands+ducts→tissue dmg+impaired mucociliary function+increased sputum viscosity→obstructs airways→lung damage→sequesters pathogens→increased infection risk→prevents digestive proteins from reaching intestines→decreases ability to absorb food+nutrients
-lungs
-pancreas
-liver
-intestines
-reproductive tract

Cystic Fibrosis (CF) Newborn Screening Programs

newborns→decreased symptomatic presentations

• hx of chronic lung dx (bronchiectasis)

• pancreatitis

• infertility

• cough

• dyspnea

• sputum production

• decreased exercise tolerance

• hemoptysis

• chronic rhinosinusitis

• diarrhea

• steatorrhea

• abdominal pain

• low BMI

• impaired growth

• clubbing

• increased anteroposterior (AP) chest diameter

• hypoxemia

• hyperresonance to percission

• crackles

• sinus tenderness

• purulent nasal secretions

• nasal polyps

• nearly all men→congenial BL absence of vas deferens+azoospermia