Title: Click here to proceed.
1Bronchiectasis
2- Chronic dilation of the bronchi marked by fetid
breath and paroxysmal coughing, with the
expectoration of mucopurulent matter.
Dorlands Illustrated Medical Dictionary 28th
Ed., W.B. Saunders Company
3(No Transcript)
4(No Transcript)
5Morphological types
- Cylindrical or tubular bronchiectasis
- Varicose
- saccular or cystic bronchiectasis
6Bronchiectasis
- Causes and pathogenesis
- Microbiology /common pathogens
- Therapeutic Goals
7Ct/cxr
8Ct/cxr
9CAUSES
10Bronchiectasis
- Worldwide, infection is the primary cause
- M. Tuberculosis
- Childhood illnesses
- Rubeola, B. Pertussis
11Infection
Inflammation
Bronchiectasis
Altered development
12Inflammation
- Characteristics across etiologies
- Persistent
- Neutrophil dominant
- Pro-inflammatory cytokines (IL-8, IL-1, TNF-a)
- Low anti-inflammatory cytokines (IL-10)
13Airway Damage Failure to Resolve Inflammation
- Inappropriate inflammation
- e.g. ABPM, CF (?)
- Impaired clearance of stimuli
- Bacteria, mucus, toxins
14Airway Damage Failure to Resolve Inflammation
- Altered Airway Milieu
- Proteolytic damage
- -e.g. cleaved receptors
- -impaired macrophage function
- Oxidant stress
- -low antioxidants associated with worse disease
- -dysregulation of signaling and cellular
function
15Childhood Infections
M. Tb.
Infection
Impaired Clearance
Inflammation
Bronchiectasis
Altered development
16Impaired Clearance
- Altered ciliary Function
- PCD, smoking, CFTR, Youngs
- Mucus rheology
- CFTR, Mucoid Ps. A
- Dilated or obstructed airways
- Impaired cough, foreign bodies, aspiration
17Impaired ImmunityIneffective inflammation
- Acquired
- Chemo-immunomodulation
- Congenital/innate
18HIV/AIDS
Chemo-Immunosuppression anti-TNF, MTX,
anti-neoplastics
Childhood Infections
M. Tb.
Innate Deficiency CGD, CVID, Igopathy (IFN)
Infection
Impaired Clearance foreign body, CF
Inflammation
Bronchiectasis
Altered development
19Chemo-Immunosuppression
HIV/AIDS
Childhood Infections
M. Tb.
Innate Deficiency
Infection
Impaired Clearance
Inflammation
Auto-Immune RA, Sjogrens, IBD ABPM
Bronchiectasis
Altered development
20Chemo-Immunosuppression
HIV/AIDS
Childhood Infections
M. Tb.
Innate Deficiency
Infection
Impaired Clearance
Inflammation
Auto-Immune ABPM
Bronchiectasis
Altered development
21Chemo-Immunosuppression
HIV/AIDS
Childhood Infections
M. Tb.
Innate Deficiency
Infection
Impaired Clearance
Inflammation
Auto-Immune ABPM
Bronchiectasis
Altered development
22BronchiectasisEpidemiology and Etiology
- Who?
- Patients - with altered immune system
- - with persistent respiratory symptoms
- Why?
- Persistent inflammation in the respiratory system
23Bronchiectasis TherapyDecrease inflammation
- antibiotics
- clearance
- Flutter, IPPV, Vest, Bronchodilators, hypertonic
saline - (anti-inflammatory chemotherapy)
- Steroids, macrolides, interferon-gamma, ibuprofen
- (surgical resection)
24When to suspect bronchiectasis?
- Chronic cough, sputum
- Coarse rales
- Persistent respiratory symptoms
- Recurrent pneumonia
- Progressive obstructive lung disease
- Funny bugs
25Clinical Characteristics
- Focal
- Sputum production
- Mild lt15 cc/d
- Moderate 15-150 cc/d
- Severe gt150 cc/d
- Hemoptysis
- Dyspnea
- Chest pain
- Systemic
- Malnutriton/wasting
- Chronic Inflammation
- gammaglobulinemia
- CRP
- Sed rate
- anemia
26Bronchiectasis TherapyAntibiotics
- Episodic or suppressive antibiotics?
-
- Yes.
- Selective pressure vs. suppression of damage
27Bronchiectasis TherapyAntibiotics
- Pro
- Decrease inflammation
- Slow progression
- Eradication?
Con Select resistance Cost Side effects adherence
difficult (e.g. Huong et al.)
28Bronchiectasis TherapyAntibiotics when to use?
- Yes
- Evidence of exacerbation
- Progressive decline
- Frequent exacerbator
- Active inflammation (?)
No Minimal disease without organism Patient
Intolerant Unaffordable
29Bronchiectasis TherapyDecrease inflammation
- Clearance
- Immunomodulatory chemotherapy
- proposed therapies
- Steroids
- Macrolides, tetracyclines
- interferon-gamma
- ibuprofen
30Bronchopulmonary Hygiene
- removal of respiratory secretions is beneficial
- chest percussion and postural drainage
- chest clapping or cupping
- inflatable vests or mechanical vibrators
- Oral devices that apply positive end-expiratory
pressure maintain the patency of the airway
during exhalation
31- Maintaining adequate systemic hydration, enhanced
by nebulization with saline, - Acetylcysteine delivered by nebulizer thins
secretions - aerosolized recombinant human DNase (rhDNase) in
patients with cystic fibrosis
32Surgery
- Localised bronchiectasis
- Proximal obstructive lesion
- Massive hemoptysis
- Recurrent infections
33Cystic FibrosisEpidemiology
- 1/2500 caucasian births (3-5 carrier rate)
- Autosomal recessive defect of CFTR
- Gene identified 1989 on Cr. 7
- 30,000 affected in USA
- 12,000 adults
- survival 31 years
34CF Genetics
- Autosomal recessive, non-lethal
- gt900 identified aberrations
- Genotypephenotype correlation poor
- Survival benefit (?)
- Heterozygote-phenotypes postulated (pancreatitis,
ABPA, MOTT bronchiectasis)
35CFTRcystic fibrosis transmembrane regulator
- chloride channel
- epithelial cells
- variable genotype - phenotype linkage
- various defects identified
- ion transport
- regulation
- processing
- production
36Results of Decreased CFTR Function
- Primary
- Increased water resorption increased mucus
viscosity - Altered cellular signaling intra/trans(?)
- (?) altered cholera toxin effects
- Secondary
- Obstruction
- Inflammation
- Dysfunction
37(No Transcript)
38Major Clinical Manifestations
- Sinusitis, polyps
- Lung
- Chronic infections
- Obstructive disease
- GI
- Insufficiency
- CFRDM
- Liver disease
- Reproductive
- Decreased fertility
3922/yo male ja Fev1 deltaF508/deltaF508
40CF respiratory pathology
- Inflammation starts as early as 4 weeks of age
- Culture negative
- BAL increased IL-8, LTB4, neutrophils,
macrophages
41CF pathologic changes
- Chronic bronchiectasis
- Obstructive lung disease
- Respiratory failure
- Transplantation/death
42The CF Diagnosis earlyor typical presentation
- Newborn screening
- Serum trypsinogen with confirmatory sweat
chloride testing - Meconium Ileus
- Failure to thrive/malabsorption
- Recurrent sino-pulmonary disease
43Diagnosis of CF
- Clinical setting
- Chronic sino-pulmonary disease
- GI / Nutritional disease
- Salt loss syndromes
- CFTR abnormality
- Abnormal sweat test
- gt 60
- Nasal potential
- Mutational analysis
- gt 2
44Vicious loops
Infection
Bronchial Obstruction
Inflammation
Bronchiectasis
45Summary
management
diagnosis
- History
- Prior infections, exposures
- Time course
- Other manifestations?
- Chest Imaging
- Define region, pattern
- Sputum culture
- Determine causal disease
- sweat testing
- immune testing
- serologic testing
- Treat bronchiectasis
- Clearance
- Antibiotics
- Immune-modulation
- Balance burden of disease vs burden of therapy
- (Sputum, Symptoms, PFTs, Weight, X-rays)
- Other
- Underlying disease therapy
- Transplantation
- Management of complications
- Collapse, plugs, hemoptysis
46Vicious loop
Antibiotics tobramycin
Infection
Bronchial Obstruction
Inflammation
Clearance Albuterol, DNase, Therapy vest
Anti-inflammatory Inhaled steroids
Bronchiectasis