Bronchiectasis

Dr Yog Raj Khinchi

Chronic Bronchitis
Definition
ADULTS: Productive cough daily
for 3 months/year for 2
consecutive years.

CHILDREN: Productive cough of

>2 months duration or recurrent
episodes of productive cough >4
times/year.
Bronchitis is a state of
increased mucus production,
with or without adequate
mucociliary transport, that
requires cough for clearance of
airway secretions.
 Airway
Stimulus/Injury

Increasing Secretion Production

Increased Effective Secretion

Mucociliary Cough Inspissation Airway
Clearance Obstruction
Recurrent/Persistent
Chronic Bronchitis: Underlying
Conditions
Chronic Airway Asthma
Infection/Inflammation: Cystic Fibrosis
Aspiration syndromes
Chronic foreign body
Tuberculosis

Primary Host Defense Ciliary dyskinesias

Abnormalities: Immunodeficiencies
Congenital
Acquired (HIV)

Inefficient Cough Airway compression

Syndromes: Trachobronchomalacia
Neuromuscular weakness
Tracheostomies
Bronchiolitis obliterans
Bronchiectasis
Pathogenesis
Airway Injury +
Secretion Stimuli

Secretion Stasis Infection

Airway Destruction +
Airway Dilation
FIGURE 2
CF vs. Idiopathic Bronchiectasis

CYSTIC IDIOPATHIC
FIBROSIS BRONCHIECTATIS

Multi-organ Involvement Sinopulmonary

Involvement
Diffuse Multifocal

Pseudomones Mouth Flora

Tenacious Secretions Mucoid/Coughable

50% Bronchodilator 50% Bronchodilator

Response Response
Progressive Outcome Variable Outcome
Treatments for Idiopathic (Post-Infectious)
Bronchiectasis
Reduce Secretion Reduce Irritant Exposure
Production: Reduce Aspiration Events
Reduce GER

Reduce Infection Exposure: Dental Hygiene

Antibiotics for: Upper Airway
Lower Airway
Exacerbations
Promote Secretion Chest Physiotherapy
Clearance:
Reduce Airway Obstruction: ?Bronchodilators
Inhaled Steroids

Prevent Infection: Immunizations

?Palivizumab, Flu shots
Pneumococcal vaccine (7 + 23 valent)
 Bronchiectasis
Irreversible, abnormal dilatation of one or more
bronchi, with chronic airway inflammation.
Associated chronic cough, sputum production,
recurrent chest infections, airflow obstruction, and
malaise
Prevalence unknown (not common)
Pathological endpoint with many underlying causes
Pathogens associated with exacerbations and
disease progression in bronchiectasis
Non-tuberculosis
Haemophilus influenzae mycobacteria
Haemophilus parainfluenzae M. avium complex (MAC)
Pseudomonas aeruginosa M. kansasii
M. chelonae
M. fortuitum
Streptococcus pneumoniae
M. malmoense
Moraxella catarrhalis M. xenopi
Staphylocccus aureus
Aspergillus-related
Stenotrophomonas maltophilia
Gram-negative enterobacter
disease
Causes / associations of bronchiectasis
Idiopathic
Postinfectious
Humoral immunodeficiency
Allergic bronchopulmonary aspergillosis (ABPA)
Aspiration/GI reflux
Rheumatoid arthritis
Youngs Syndrome
Cystic Fibrosis
Ciliary dysfunction
Ulcerative colitis
Panbronchiolitis
Congenital
Yellow nail syndrome
 Evidence for dysregulated immunity in
bronchiectasis
Increased susceptibility to infection - bacterial, non-
tuberculous mycobacterial (NTM), and aspergillus-related
lung disease
Associated with autoimmune disease such as the
inflammatory bowel disease, ulcerative colitis
Neutrophils are markedly raised, as predicted from high local
levels IL-8
Associated with immune deficiency syndromes such as TAP
deficiency syndrome
 Evidence for dysregulated immunity in
bronchiectasis
Increased susceptibility to infection - bacterial, non-
tuberculous mycobacterial (NTM), and aspergillus-related
lung disease
Associated with autoimmune disease such as the
inflammatory bowel disease, ulcerative colitis
Neutrophils are markedly raised, as predicted from high local
levels IL-8
Associated with immune deficiency syndromes such as TAP
deficiency syndrome
 Bronchiectasis associated with increased
susceptibility to specific pathogens
Non-tuberculosis
Haemophilus influenzae mycobacteria
Haemophilus parainfluenzae M. avium complex (MAC)
Pseudomonas aeruginosa M. kansasii
M. chelonae
M. fortuitum
Streptococcus pneumoniae
M. malmoense
Moraxella catarrhalis M. xenopi
Staphylocccus aureus
Aspergillus-related
Stenotrophomonas maltophilia
Gram-negative enterobacter
disease
 Evidence for dysregulated immunity in
bronchiectasis
Increased susceptibility to infection - bacterial, non-
tuberculous mycobacterial (NTM), and aspergillus-related
lung disease
Associated with autoimmune disease such as the
inflammatory bowel disease, ulcerative colitis
Neutrophils are markedly raised, as predicted from high local
levels IL-8
Associated with immune deficiency syndromes such as TAP
deficiency syndrome
Bronchiectasis associated with
autoimmune disease

Rheumatoid arthritis
Systemic lupus erythematosus
Relapsing polychondritis
Inflammatory bowel disease -
Ulcerative colitis and Crohns
disease
 Evidence for dysregulated immunity in
bronchiectasis
Increased susceptibility to infection - bacterial, non-
tuberculous mycobacterial (NTM), and aspergillus-related
lung disease
Associated with autoimmune disease such as the
inflammatory bowel disease, ulcerative colitis
Neutrophils are markedly raised, as predicted from high local
levels IL-8
Associated with immune deficiency syndromes such as TAP
deficiency syndrome
 Suppurative Lung Disease
Bronchiectasis
Lung abcess
Empyema
 Brochiectasis
Def:destructive lung disease :chronic permanent and
abnormal dilatation of bronchial wall with variable
inflammatory process in the lung. Chronic bronchial
sepsis
Pathology: non-inflammatory:congenital
acquired:
Bronchial wall dilatation.
excess mucus.
loss of connective tissue support
inflammation with metaplasia of ciliated
epithelium to squamous or columnar + micro-abcess formation.
Collapsibility of the wall leads to obstructive defect on spirometry.
 Notes
Bronchiectasis is of two types:
1- Dry: there is dilatation, destruction,
but no purulent secretion.
2- Suppurative (refers to chronic
bronchial sepsis): this is
bronchiectasis that have suppuration
( pus formation).
 Pathogenesis
Vicious cycle:
infectious insult & impaired drainage &/or defect in host defence

Role of positive :
genetic susceptibilty
family history
 Notes
Normally, in healthy individuals the immune system and
mechanical system (cilia function) are intact, resulting in
good clearance of microorganisms leading to recovery.
Therefore, with impaired cilia function and/or host defense
a vicious cycle (ongoing inflammation) will occur leading to
bronchiectasis.
People with family history and genetic susceptibility (e.g a-
1 antitrypsin deficiency), when having a microbial insult,
they can not clear it probably because of defective immune
and/or mechanical drainage system.
The most important organisms are: H.influenza,
encapsulated streptococcus pneumoniae, and
pseudomonus.
 Classification
Spectrum:
1.follicular cylindrical:transmural inflammation, loss of bronchial
elastic tissue, mucosal edema; post infectious
2.Saccular:ulceration ,craters; general dilatation specially terminal
(saccules).
(varicose:distortion by scarring and obstructions)
3. Atelactatic:
localised, could be secondary to 1, or 2.importance to site and
distribution: lobar or segmental.
 Notes
Another type of classification is:
1- follicular cylindrical: it is called follicular
because of presence of lymphoid follicles in the
bronchus. But it is generally called cylindrical
because it is transmural and localized to one
bronchus.
2- saccular: so called because there are succule
like formation at the terminal part of the
bronchus.
- varicose: this is when you have two types
together cylindrical and saccular.
 Causes of bronchiectasis

Congenital:elastic bronchial wall def.

other congenital abnormalities,lung sequestration

Mechanical bronchial obstruction:

Intrinsic and extrinsic:
Lymph node or scaring :post-TB
Foreign body: selective lobes
Child vs adult
 Notes
Causes:
1- congenital:in fetus, the lung is not mature enough because
its blood supply is deprived, therefore making it liable to
bronchiectasis.
2- bronchial obstruction: the process of obstruction will cause
stagnation of secretion which will then start the process of
microbial infection leading to abcess formation and then
tissue destruction, hence bronchiectasis.
- Bronchial obstruction can be intrinsic (in wall or lumen) or
extrinsic (external compression).
 Contd Notes
- TB produces both intrinsic (by scarring) and extrensic
(compression by lymph node).
The common site of obstruction is the right posterior upper
lobe.
Obstruction of airways in children can be caused by inhaling
a foreign body, and the inhalation of a foreign body also
leads to lung abcess.
Obstruction in adults can occur due to inhaling chemicals or
impaired gastroesophageal reflex and aspiration.
 *Contd Causes
*Inflammatory pneumonitis
-Aspiration:chemical ,gastric
-Inhalation: fumes

*Granulomata and fibrosis:

sarcoidosis ,TB,IPF

*Immunological over-response: ABPA (allergic bronchial pulmonary

aspergellosis), post lung transplant

*Immune deficiency
Primary: children: hypogammaglobinaemia:repeated
sinopulmonary infection
Secondary: AIDS, CA
 Contd Causes
*Mucociliary clearance defects
-Genetic
-Primary ciliary dyskinesia :cilia abnormal
50% Kartegners:S.I, sinusitis Bronchiectasis.
-Cystic Fibrosis: abnormal mucus content.
*Acquired: -Youngs: sinusitis ,bronchiectasis ,obstructive azoospermia.
Abnormal mucus.
- -Post-infective bronchial damage:measles, pertussis.
MAI.Viral.Mycoplasma
- Toxins: SO2,smoking, lidocaine. Asthma.
*Rheumatic and systemic inflammatory diseases:e.g IBD (inflammatory
bowel disease).
*Idiopathic (including diffuse panbronchiolitis), good % with no cause
 Notes
In cystic fibrosis, the cilia is normal but the mucus is
abnormal because there is a block in the chlorine
channel (not responsive to cyclic AMP) causing the
mucus to become more sticky. This disease is
characterized by increased Na and Cl in sweat, which is
detected by sweating test.
Kartegner syndrome: is a type of primary ciliary
dyskinesia which is also associated with sinusitis,
bronchiectasis, and transposition of the viscera.
Youngs disease is characterized by high lipid content of
mucus.
Idiopathic: panbronchiolitis (responsive to macrolide) is
found mainly in Japanese and East Asia.
 Conts Notes
ABPA causes hyper immune activity.
Atypical mycobacterial infection and
uncontrolled asthma can cause
abnormal cilia.
 *Mucociliary clearance defects
*Genetic: Cystic fibrosis: AR, Gene
mutation,chromosome 7,Transmembrane conductance
regulator pr-CFTR
commonest:deletion at 508
impairment of chloride channel.non respondent cyclic-
AMP. Cl- and water not excreted but Na and its water
absorbed ,mucus get thickened.Sweat content of Na , Cl
altered.
 Clinical manifestation of cystic fibrosis

Primary
Bronchiectasis *Nasal polyps
Bronchiolitis, bronchitis * Cirrhosis
Infertility * Meconium ileus
Pancreatic insufficiency
Pneumonia
Salt loss
 Secondary
*Atelectasis * Allergic bronchopulmonary
*Clubbing aspergillosis
*Malabsorption * cholelithiasis
*Heat prostration * Cor pulmonale
*Hypochloraemic * Conductive hearing loss
hypokalaemic alkalosis * Diabetes mellitus
 Diagnosis of Bronchiectasis
1.History: usually :muco-purulent sputum, cough.
occasionally recurrent hemoptysis, recurrent fever
Less specific : dyspnea, wheeze ,pleuritic pain
2.Examination: Early: normal

nowadays:clubbing 3%,crackles70%
rarely :Core pulmonale( right ventricular
hypertrophy due to pulmonary hypertension),CCF.
 Notes
The most important sign is is abundant productive cough
increasing with lying down.
The second important manifestations are lung abcess,
infective emboli, clubbing and amyloidosis (AA type).
How hemoptysis occurs?
An insult causes injury, followed by healing and
neovascularization. These new formed blood vessels are
weak and fragile, hence easily ruptured causing
hemoptysis.
- Wheeze: musical sounds produced by air passing through
narrowed airways (during inspiration & expiration).
- Crackles (crepitations): non-musical sounds mainly heard
during inspiration caused by reopening of occluded small
airways.
 Investigation
Sputum: gram stain,selective media ( it is done not to
miss certain organisms),semi quantitative
!!TB, fungal
CXR: early volume loss,vascular crowdening
late:cylindrical tramline,cystic.
Disribution: central ABPA,
LL: idiopathic
UL: CF or variant
 Investigation
Bronchogram: surgery
HRCT: standard
Sinus X-Ray
PFT: normal,obstructive,air trapping
Specific: Ig level:IgA (in immunocompromised
patients).
precipitin level is measured in skin, sputum and serum. If it
is high in 2 out of the 3 sites, we think of ABPA.
Brochoscopy
 Notes
Bronchogram: do a bronchoscope then inject a
dye. It is done when you are planning for
surgery.
HRCT= high resolution CT scan.
Sinus X-ray is done to rule out sinusitis
PFT is early normal, later:obstruction/ air
trappin
Bronchoscopy is indicated in case of hemoptysis
and it is important to rule out obstructive
lesions (e.g. foreign bodies) and TB. These
three conditions are not responding to
antibiotics.
 Notes
The previous slide shows CT taken
during inspiration.
Usually, a blood vessel has a
bronchus beside it that has the same
size.
So, if you see a bronchus larger than
the accompanied vessel then suspect
bronchiectasis.
 Notes
The previous CT was taken for the
same patient during full expiration,
which is better than the full
inspiratory CT.
 Contd investigation
UGI Endoscopy
Anti protease level
Sweat test
Genetic studies
Rh. Factor
 Complication
Mostly: infective
exacerbation,haemoptysis
Rarely now: metastatic spread of
infection empyema
amyloidosis clubbing
joint pain
Note: certain complications are rare because of early
detection.
 Management
Prevention:
Medical treatment:control infection ,bronchial hygiene
Antibiotic:acute exacerbation: cover I.infl., strep.
Prophylactic:several protocols: commoner :
10days/Month or 10 days alternate with 10 free days.
Bronchodilator
IV Ig if deficient
Oral Steroid:only ABPA vs inhaled steroids
Mucolyte :debatable.role of ACC ( N-acetylcystin
which is antioxidant), DNAs
Anti-fungal :itracanazole: ABPA
Future treatment:Antiprotease replacement
CF treatment (very complicated)
 Notes
Management of bronchiectasis includes:
- 1- Giving Igs for immunocompromised patients.
- 2- Vaccination for H. influenza, pneumococcus and
influenza.
- 3- Screening for TB (very important).
- 4- Bronchodilators (almost always given).
- 5- Steroids (only for ABPA because of the
hyperimmunity).
- 6- mucolytics: make sputum more liquid and less viscus
(not important except DNAs in cystic fibrosis patients to
improve their lung function).
 Contd management
Physiotherapy
Corner stone:Postural drainage,
hydration ,nebulized saline
*Surgery:
.Massive haemoptysis: > 600ml/day.
.Localized troublesome resectable bronchiectasis
.Palliative for important stump.
 Notes
- physiotherapy: teach the patient how to drain his lung
(lungs should be drained daily).
- Surgery: is indicated:
1- when there is severe hemoptysis
2- if one lobe causing problems to the patient, so you
resect it to prevent damage to other lobes
3- if you have a diffuse lung disease and one particular area
which is more problematic, then you resect it.
- Mild hemoptysis: loss of 200-300ml/day.
- Moderate hemoptysis: loss of 300-600ml/day.
- Severe hemoptysis: loss of > 600ml/day.
 Contd management
Haemoptysis:
*Mild: antibiotic
*Severe: surgery or bronchial artery embolization
Lung Transplant: always double.
- Indication for transplantation: bilateral, advanced, and
bleeding bronchiectasis.
- 2 lungs should be transplanted because if you transplant
one lung only, the diseased lung you left in the body can
affect the new transplanted lung to become also
infected.
Bronchiectasis
Chronic dilation of the bronchi marked by
fetid breath and paroxysmal coughing, with
the expectoration of mucopurulent
matter.
 Morphological types
Cylindrical or tubular bronchiectasis

Varicose

saccular or cystic bronchiectasis

Bronchiectasis

Causes and pathogenesis

Microbiology /common pathogens
Therapeutic Goals
Ct/cxr
Ct/cxr
 Bronchiectasis
Worldwide, infection is the primary cause
M. Tuberculosis
Childhood illnesses
Rubeola, B. Pertussis
Childhood Infections M. Tb.

Infection

Inflammation

Bronchiectasis

Altered development
 Inflammation

Characteristics across etiologies:

- Persistent
- Neutrophil dominant
- Pro-inflammatory cytokines (IL-8,
IL-1, TNF-a)
- Low anti-inflammatory cytokines
(IL-10)
 Airway Damage
Failure to Resolve Inflammation

Inappropriate inflammation
e.g. ABPM, CF (?)

Impaired clearance of stimuli

Bacteria, mucus, toxins
 Airway 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
Childhood Infections M. Tb.

Infection

Inflammation* Impaired Clearance

Bronchiectasis

Altered development
 Impaired Clearance
Altered ciliary Function
PCD, smoking, CFTR, Youngs

Mucus rheology
CFTR, Mucoid Ps. A

Dilated or obstructed airways

Impaired cough, foreign bodies, aspiration
 Impaired Immunity
Ineffective inflammation

Acquired
Chemo-immunomodulation
Congenital/innate
 HIV/AIDS Chemo-Immunosuppression
anti-TNF, MTX, anti-neoplastics

Childhood Infections M. Tb.

Innate Deficiency
CGD, CVID, Igopathy (IFN)

Infection

Inflammation Impaired Clearance

foreign body, CF

Bronchiectasis

Altered development
 HIV/AIDS Chemo-Immunosuppression

Childhood Infections M. Tb.

Innate Deficiency

Infection

Auto-Immune Impaired Clearance

RA, Sjogrens, IBD Inflammation
ABPM

Bronchiectasis

Altered development
 HIV/AIDS Chemo-Immunosuppression

Childhood Infections M. Tb.

Innate Deficiency

Infection

Auto-Immune Inflammation Impaired Clearance

ABPM

Bronchiectasis

Altered development
 HIV/AIDS Chemo-Immunosuppression

Childhood Infections M. Tb.

Innate Deficiency

Infection

Auto-Immune Inflammation Impaired Clearance

ABPM

Bronchiectasis

Altered development
 Bronchiectasis
Epidemiology and Etiology

Who?
Patients - with altered immune system
- with persistent respiratory symptoms

Why?
Persistent inflammation in the respiratory system
 Bronchiectasis Therapy
Decrease inflammation

antibiotics
clearance
Flutter, IPPV, Vest, Bronchodilators, hypertonic saline

(anti-inflammatory chemotherapy)
Steroids, macrolides, interferon-gamma, ibuprofen

(surgical resection)
 When to suspect bronchiectasis?

Chronic cough, sputum

Coarse rales
Persistent respiratory
symptoms
Recurrent pneumonia
Progressive obstructive lung
disease
Funny bugs
 Clinical Characteristics

Focal Systemic
Sputum production Malnutriton/wasting
Mild <15 cc/d Chronic Inflammation
Moderate 15-150 gammaglobulinemia
cc/d CRP
Sed rate
Severe >150 cc/d
anemia
Hemoptysis
Dyspnea
Chest pain
 Bronchiectasis Therapy
Antibiotics

Episodic or suppressive antibiotics?

Yes.

Selective pressure vs. suppression of damage

 Bronchiectasis Therapy
Antibiotics

Con
Pro Select resistance
Decrease inflammation Cost
Side effects
Slow progression adherence difficult (e.g.
Eradication? Huong et al.)
 Bronchiectasis Therapy
Antibiotics

Con
Pro Select resistance
Decrease inflammation Cost
Side effects
Slow progression adherence difficult (e.g.
Eradication? Huong et al.)
 Bronchiectasis Therapy
Antibiotics when to use?

No:
Yes: Minimal disease without
Evidence of organism
Patient Intolerant
exacerbation
Unaffordable
Progressive decline
Frequent
exacerbator
Active inflammation
(?)
 Bronchiectasis Therapy
Decrease inflammation

Clearance
Immunomodulatory chemotherapy
proposed therapies:
Steroids
Macrolides, tetracyclines
interferon-gamma
ibuprofen
 Bronchopulmonary 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
 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
 Surgery
Localised bronchiectasis
Proximal obstructive lesion
Massive hemoptysis
Recurrent infections
 Vicious loops
Infection

Bronchial
Obstruction Inflammation

Bronchiectasis
 Summary
diagnosis management
History Treat bronchiectasis
Prior infections, exposures Clearance
Time course Antibiotics
Other manifestations? Immune-modulation
Chest Imaging Balance burden of disease vs
Define region, pattern burden of therapy
Sputum culture (Sputum, Symptoms, PFTs, Weight, X-rays)
Determine causal disease Other
sweat testing Underlying disease therapy
immune testing
serologic testing Transplantation
Management of complications
Collapse, plugs, hemoptysis
 Antibiotics
Vicious loop tobramycin
Infection

Bronchial
Obstruction Inflammation
Clearance Anti-inflammatory
Albuterol, DNase, Inhaled steroids
Therapy vest

Bronchiectasis
 Bronchiectasis

Dilated airways with frequently

thickened walls
 Bronchiectasis: Clinical

Note: Bronchiectasis may happen 2/2 COPD or may be a

separate process with very similar symptoms

Clinical:
Cough (90 %)
Daily sputum production (76%)
Dyspnea (72%)
Hemoptysis (56%)
Recurrent pleurisy
 Pathophysiology
2 Prerequisites:

Infectious insult

Impairment of drainage, airway obstruction,

and/or a defect in host defense.
 Pathophys Continued
Infection:
Bacterial, mycobacterial, esp. ABPA central airway
bronchiectasis

Airway obstruction:
intraluminal tumor, foreign body, lymph nodes, COPD

Immunodeficiency:
ciliary dyskinesia, HIV, hypogammaglobulinemia, cystic fibrosis
(obstruction and immunodef.)
Characteristic central bronchiectasis 2/2 ABPA
Note characteristic location in the upper lobes and superior segments of
lower lobes
 Exacerbation: Etiology +Rx
Colonization/infection:
Hemophilus
Pseudomonas
MAI
Aspergillus

Very difficult to distinguish colonization from acute infection with these

bugs.
Psuedomonas colonized more bronchiectasis on CT; increased number
of hospitalizations vs H. flu colonization
Effect of sputum bacteriology on the quality of life of patients with bronchiectasis. Wilson CB; Jones PW; O'Leary CJ; Hansell DM; Cole PJ; Wilson R Eur
Respir J 1997 Aug;10(8):1754-60.

Treatment:
fluoroquinolone
 Prevention
Antibiotics-Controversial:
Consider Macrolide TIW
Cipro qd X 7-14 D/ month

Bronchial Hygiene, physiotherapy, pulmonary

rehab
?bronchodilators, and steroids
Surgery
 CXR
08/21
 CXR
08/23
 CXR
08/28
 CXR
08/31
HRCT
08/31
 CXR
09/01
 CXR
09/09
 CXR
09/15
Bronchiectasis
 Introduction
Chronic daily cough w/ viscid sputum
Bronchial wall thickening and luminal dilation
on CT
Prevalence varies
Associated w/ age, female
Management
Infection control
bronchial hygiene
Surgical resection in selected pt
 Pathophysiology
Permanent abnormal dilation and destruction
of bronchial walls
Two factors
Infection
Impairment of drainage, airway obstruction,
and/or defect in host defense
Biomarkers: inflammatory cells or 8-iso-
prostaglandin F(2) in sputum
 Etiology
Pulmonary infections
viral, mycoplasma, TB, MAC
Airway obstruction
Defective host defenses
ABPA (allergic bronchopulmonary aspergillosis)
Rheumatic and other systemic dz
RA, Sjogrens syndrome
Ulcerative colitis
Dyskinetic cilia
Cystic fibrosis rare in TW
Cigarette smoking?
 Diagnostic Evaluation
CBC w/ differential
Ig quantification
Sputum culture and smear
bacteria, mycobacteria, fungi
CXR
Linear atelectasis, tram track, ring shadow,
irregular peripheral opacities
HRCT: defining test
PFT
CXR of Bronchiectasis
CXR of Bronchiectasis

Hansell DM - Radiol Clin North Am - 01-JAN-1998; 36(1): 107-28

CXR of Bronchiectasis

Hansell DM - Radiol Clin North Am - 01-JAN-1998; 36(1): 107-28

 HRCT
Sensitivitiy ~97%
Findings
Airway dilation
Lack of tapering of bronchi
Bronchial wall thickening
Mucopurulent plugs or debris
Cyst
Pneumonia, LAP, emphysema
Distributions
Upper lobe
Central distribution
HRCT

Radiol Clin N Am 43(2005) 513-542

HRCT
HRCT
 Management
Infection control
bronchial hygiene
Surgical resection in selected pt
 Infection Control
Acute exacerbation
viscous, dark sputum, lassitude, SOB, pleurisy
Fevers and chills generally absent
CXR rarely show new infiltrates
H. influenzae and P. aeruginosa
FQ is reasonable (eg. ciprofloxacin) for 7~10 days
 Prevention
Daily ciprofloxacin (500~1500mg) in 2~3 doses
Macrolide daily or three times weekly
Daily use of a high dose oral antibiotic, such as
amoxicillin 3 g/day
Aerosolization of an antibiotic
Intermittent intravenous antibiotics
 Problematic Pathogen
Pseudomonas aeruginosa
Almost impossible to irradicate
Wilson CB et al.
Reduced QoL
More extensive bronchiectasis on CT
Increased number of hospitalizations
Ciprofloxacin quickly develops resistance
 Bronchial Hygiene
Oral hydration
Nebulization
Normal saline
Acetylcyteine
Recombinant DNAase
Hypertonic saline, mannitol, dextran, lactose
Physiotherapy
Chest percussion
Prone position
Bronchodilator? Steroid? NSAID?
 Surgical Intervention
Removal of the most involved segments
Most common: middle and lower lobe
resecton
Hemoptysis:
Bronchial a. embolization
Lung transplantation
 Lung Transplantation
Overall 1-year survival : 68% (54-91%)
Overall 5-year survival : 62% (41-83%)
Subgroup
SLTX : 1 yr survival 57% (20%-94%) n=4
Mean FEV1 : 50% predicted (34%-61%),
Mean FVC : 53% predicted (46-63%)
2 lungs : 1 yr survival 73% (51-96%) n = 10
Mean FEV1 : 73% predicted (58%-97%),
Mean FVC : 68% predicted (53%-94%)
 Chapter 14
Bronchiectasis

A
B
E

Figure 141. Bronchiectasis. A, Varicose bronchiectasis. B, Cylindrical bronchiectasis. C, Saccular

bronchiectasis. Also illustrated are excessive bronchial secretions (D) and atelectasis (E), which are
both common anatomic alterations of the lungs in this disease.
 Three Forms of Bronchiectasis
Varicose bronchiectasis
Cylindrical bronchiectasis
Saccular bronchiectasis
 Anatomic Alterations of the Lungs

Chronic dilation and distortion of bronchial airways

Excessive production of often foul-smelling sputum
Smooth muscle constriction of bronchial airways
Hyperinflation of alveoli (air-trapping)
Atelectasis, consolidation, and parenchymal fibrosis
Hemorrhage secondary to bronchial arterial erosion
 Etiology
Acquired bronchiectasis
Recurrent pulmonary infection
Bronchial obstruction
Congenital bronchiectasis
Kartageners syndrome
Hypogammaglobulinemia
Cystic fibrosis
 Overview of the Cardiopulmonary
Clinical Manifestations Associated
with BRONCHIECTASIS
The following clinical manifestations result from
the pathophysiologic mechanisms caused (or
activated) by Atelectasis (see Figure 9-12),
Consolidation (see Figure 9-8), Bronchospasm
(see Figure 9-10), and Excessive Bronchial
Secretions (see Figure 9-11)the major anatomic
alterations of the lungs associated with
bronchiectasis (see Figure 14-1).
Figure 9-7. Atelectasis clinical scenario.
Figure 9-8. Alveolar consolidation clinical scenario.
Figure 9-9. Increased alveolar-capillary membrane thickness clinical scenario.
Figure 9-10. Bronchospasm clinical scenario (e.g., asthma).
Figure 9-11. Excessive bronchial secretions clinical scenario.
 General Management of
Bronchiectasis
General treatment includes:
Controlling pulmonary infections
Controlling airway secretions
Preventing complications
 General Management of
Bronchiectasis
Respiratory care treatment protocols
Oxygen therapy protocol
Bronchopulmonary hygiene therapy protocol
Hyperinflation therapy protocol
Aerosolized medication protocol
Mechanical ventilation protocol
 General Management of
Bronchiectasis
Other medications commonly prescribed
by the physician
Xanthines
Expectorants
Antibiotics
 BRONCHIECTASIS
RADIOLOGICAL FEATURES
 BRONCHIECTASIS
THE CHEST RADIOGRAPH
Often normal if not severe
Too many white lines extending from the hila
= tram-tracks
Elongated (tubular) opacities (white)
Small circles containing air (black) or fluid and
air (air-fluid level)
MILD BRONCHIECTASIS
Normal chest radiograph
presents with hemoptysis
MODERATE BRONCHIECTASIS
- Coarse white lines
extending out from hila
TOO MANY WHITE LINES
SEVERE BRONCHIECTASIS
SEVERE BRONCHIECTASIS

Circle filled
with air
SEVERE BRONCHIECTASIS
RINGS (CYSTS) CONTAINING AIR-FLUID LEVELS
 BRONCHIECTASIS
THE CT SCAN
Signet ring sign
Tram-tracks
String of beads
Circles filled with air or air and fluid
Tubular and branching opacities
Bronchi visible within 1 cm of the pleura
Scarring
 Normal pulmonary
artery (pearl)

Dilated bronchus
(ring)

SIGNET-RING SIGN
 Dilated bronchus

BRONCHIECTASIS
Bronchi visible
within 1 cm of
the pleura

String
of beads

BRONCHIECTASIS
 Destroyed
lung
(Scarring)

BRONCHIECTASIS
 CAUSES OF BRONCHIECTASIS
Congenital
Acquired
 CONGENITAL CAUSES OF
BRONCHIECTASIS
Cystic fibrosis
Immotile cilia syndrome
 CYSTIC FIBROSIS
Diffuse bronchiectasis
Most severe in the upper lobes
CYSTIC FIBROSIS
 Worse in the
upper lung
zones

CYSTIC FIBROSIS
 IMMOTILE CILIA SYNDROME
Diffuse bronchiectasis
May have situs inversus (Kartageners
syndrome
 Bronchiectasis

Dextrocardia

KARTAGENERS SYNDROME
 Bronchiectasis

KARTAGENERS SYNDROME
KARTAGENERS SYNDROME
KARTAGENERS SYNDROME

Dextrocardia

Dilated
bronchus
 CAUSES OF ACQUIRED
BRONCHIECTASIS
Post-infectious
Post-obstructive
aspirated foreign body
slow-growing tumour
 POST-INFECTIOUS
BRONCHIECTASIS
Affects the part of the lung which was
involved with pneumonia
Often diffuse as most commonly secondary to
a viral pneumonia
 POST-OBSTRUCTIVE
BRONCHIECTASIS
Focal or localized because only distal to the
obstructing lesion
Dilated bronchi distal to obstruction filled
with mucus instead of air
FOCAL BRONCHIECTASIS
FOCAL BRONCHIECTASIS

Branching
tubular opacities
FOCAL
BRONCHIECTASIS
Focal bronchiectasis
due to slow-growing
endobronchial tumour
Focal bronchiectasis
due to slow-growing
endobronchial tumour

Dilated bronchi
filled with mucus

Branching
tubular opacity
Dilated bronchi
filled with mucus
instead of air due to
proximal obstruction
PULMONARY EMBOLISM

RADIOLOGICAL FEATURES
 Lung - Pathology

Acute Lung Injury

Pulmonary edema

ARDS (Diffuse alveolar damage)

Acute interstitial pneumonia

 Pulmonary Edema
1. Hemodynamic disturbances( capillary hydrostatic pressure), MCC-
LVF, Heart failure cells
2. oncotic pressure (Hypoalbuminemia) Renal failure,
Malnutrition, Cirrhosis
3. Microvascular injury - capillary permeability,
Seen in ARDS following
a) Infection -viral pneumonia
b) Gases, Aspiration, Drugs--heroin, Paraquat (herbicide)
c) Shock, Trauma, Sepsis, DIC
ARDS:
Also known as ***Diffuse Alveolar Damage (DAD) pulmonary
edema (protein rich) hyaline membrane disease hypoxemia
(refractory to oxygen Rx )
Mortality in 50% of cases
Clinical Manifestations: respiratory insufficiency, Cyanosis, arterial
hypoxemia multi-organ failure
Acute interstitial pneumonia Cause is unknown (Unlike
ARDS) but Radiographic and Pathologic features, mortality similar to
ARDS
 Bronchiectasis
Infection + permanent dilatation of bronchi
Causes:
infections and causes of bronchial obstruction (FB,
mucus plugs, tumors, sequestrations, cystic fibrosis)
immotile cilia (Kartageners )syndrome (Bronchiectasis,
dextrocardia -situs inversus, chronic sinusitis, and
infertility)
Clinically:
Chronic cough, productive of purulent sputum
Dyspnea and orthopnea in severe cases
later obstructive respiratory insufficiency & Corpulmonale
 Bronchiectasis
Gross

Distended peripheral
bronchi (Due to weakening
of wall)
Bronchiectasis
Gross
PRIMARY ANTIBODY
DEFICIENCY
(PAD)
&
BRONCHIECTASIS
(UKPIN / BTS GUIDELINES)
 BRONCHIECTASIS
A destructive lung disease characterised by:

Abnormal & permanent dilatation of medium sized bronchi

An associated, persistent and variable inflammatory process

producing damage to bronchial elastic and muscular
elements
 PATHOLOGY

Neutrophil proteases
(acute infection in a normal or compromised host)

Epithelial injury
+
Structural protein damage

Damaged, dilated airway

Mucous retention / chronic, recurrent infection

Ongoing inflammation / tissue damage / repair
 BRONCHIECTASIS - aetiology
Infection
- pertussis, influenza, measles, TB, necrotising peumonia
Bronchial obstruction
- mucoid impaction, ABPA
Congenital anatomical lung abnormality
Inherited disorders
- ciliary dysfunction
- cystic fibrosis
- alpha-1 AT deficiency
Undefined (29 - 49%)
BRONCHIECTASIS OF UNDEFINED
REF.
AETIOLOGY NOS. ANALYTE % age ABN.

Hilton & Doyle 53 IgG/A/M 0 -

1978
Murphy et al 23 IgG/A/M, Gsub 0 -
1984
Barker et al 30 IgG/A/M, Gsub 37 Panhypo (9/30)
1987 IgM (2/30)
De Gracia et al 65 Gsub, Hib 48 IgG2
1996 Hib (10/19)
Hill et al 89 Gsub 6 IgG4
1998
Stead et al 56 IgG/A/M, Gsub 23 IgG4
2002 Hib, Pneum Pneum (1/29)
 BRONCHIECTASIS
Pasteur et al. Am J Respir Crit Care Med (2000) 162, 1277-1284

ASSOCIATION n %
Idiopathic 80 53
ABPA 11 7
PAD 11 7
Neutrophil defect 1 <1
Rheumatoid disease 4 3
Ulcerative colitis 2 <1
Ciliary dysfunction 3 1.5
Youngs syndrome 5 3
Cystic fibrosis 4 3
Post-infectious 44 9
Aspiration/reflux 6 4
Other defineable 2 <1
 BRONCHIECTASIS in PAD
CVID
53% (Hausser et al 1983)
44% (Watts et al 1986)
18% (Hermazewski & Webster 1993)
20% (UK PAD Audit 1993-96)
27% (chronic lung disease) (Cunningham Rundles 1999)
58% (Garcia 2001)
43% (Busse et al 2002)

XLA
7% (Hermazewski & Webster 1993)
12% (UK PAD Audit 1993-96)
20% (Quartier et al 1999)
RESPIRATORY INFECTIONS

Figure 2 Types of infection in the 37 patients receiving

immunoglobulin replacement treatment. The numbers of each type
of infection are listed by each chart section.
 DIAGNOSTIC DELAY
Average: diagnosis - 6.3 years
treatment - additional 3.9
Diagnostic delay > 2 years: risk of bronchiectasis
sinusitis
iron deficiency
(UK PAD Audit 1993-96) 3

Strongest predictor of chronic pulmonary disease in treated

patients is established lung disease at time of presentation
n= XLAx10, CVIDx12
IMIg x 18, IVIg x 3, FFP x 1 (all + daily antibiotic)
(Sweinberg et al 1991) 3
 UK PAD AUDIT 1993-96
Development of bronchiectasis following diagnosis:

<1980 1981-87 >1988

77% 70% 42%
CHRONIC LUNG DISEASE in PAD

Damage sustained prior to active treatment

and/or

Continued inflammation despite treatment

 AIMS
Define evidence-based guidelines relevant to:

investigation level appropriate to screen for

significant antibody deficiency in all patients with
bronchiectasis

diagnosis & management of bronchiectasis

complicating primary antibody deficiency
 GUIDELINES
Simple
Evidence-based
Consistent with existing,
recognised standards
Realistic
Explicit
Clear & well documented
Credible & widely supported
Results orientated (outcomes)
Valid
Reproducible
Reliable
Involving & representative of
key disciplines
Clinically applicable
Clinically flexible
Scheduled for review
 GUIDELINES
LITERATURE REVIEW
Meta-analyses
Systematic reviews
RCTs
Longitudinal studies
Case control/cohort studies
Case reports/case series
Expert opinions
DATABASES
Ovid Online Collection
- Medline, preMedline
- CINAHL, EMBASE
- Journals@ovid
EBM Reviews
- Cochrane Systematic Reviews
- Cochrane Controlled Trials
- Effectiveness Reviews Abstracts
- ACP Journal Club
Allied & Complementary
Medicine
Specialty Contacts
 GUIDELINES
EVIDENCE RECOMMENDATION
1 A
2 B
3 C
4 D
(Good Practice Points)
SIGN, RCPCH, BTS
 DIAGNOSIS
PRIMARY ANTIBODY DEFICIENCY

Humoral abnormalities are common in bronchiectasis 3

Respiratory Physician + Immunologist 4
Diagnosis of significant antibody deficiency should entail use of
established and widely accepted criteria: 4

- Primary Immunodeficiency Diseases. Report of an IUIS Scientific Group

Clinical & Experimental Immunology 1999 (118), Suppl 1:1-34
- Diagnostic Criteria for Primary Immunodeficiencies.
Clinical Immunology 1999 (93), 190-197
- Practice parameters for the Diagnosis & Management of Immunodeficiency.
Annals of Allergy, Asthma & Immunology 1996 (76), 282-294
 PFTs
- Reversible/irreversible bronchial obstruction
- Granulomatous disease etc.

Correlate poorly with Radiology (bronchiectasis) 3

- Pulmonary abnormalities in patients with primary hypogammaglobulinaemia
Kainulainen et al. Jounal of Allergy & Clinical Immunology (1999) 104, 1031-1036
- Pulmonary manifestations of hypogammaglobulinaemia
Dukes et al. Thorax (1978) 33, 603-607
- Radiologic findings of adult primary immunodeficiency disorders: contribution of CT
Obregon et al. Chest (1994) 106, 490-495

Static volumes/flow-volume loops

RADIOLOGY - CXR
Bronchiectasis

- vessel crowding
- loss of vessel markings
- tramline/ring shadows
- cystic lesions/ air-fluid levels
- evidence of TB

Poor:
diagnostic sensitivity
monitoring of progression
3
RADIOLOGY - HRCT
- bronchial dilatation
- bronchial wall thickening
- classification (pathology)

sensitivity (97%) > CXR 3

chromosomal radiosensitivity
- plain CXR (x 3 days background)
- HRCT: x 30-40
- conventional CT: x 200
? routine baseline
? (a)symptomatic monitoring
 UNSUSPECTED DISEASE
(Clinical v CXR v HRCT)

Bronchiectasis in Hypogammaglobulinaemia - A Computed

Tomography assessment. Curtin et al. Clinical Radiology (1991) 44, 82-84
Radiologic Findings of Adult primary Immunodeficiency Disorders.
Obregon et al. Chest (1994)106, 490-495
Chest High Resolution CT in Adults with Primary Humoral
Immundeficiency. Feydy et al. British Journal of Radiology (1996) 69, 1108-1116
Clinical Utility of High-Resolution Pulmonary Computed Tomography
in Children with Antibody Deficiency. Manson et al. Pediatric Radiology (1997)
27, 794-798
The Value of Computed Tomography in the Diagnosis & Management
of Bronchiectasis. Pang et al. Clinical Radiology (1989) 40, 40-44
Review Article: Imaging in Bronchiectasis. Smith et al. British Journal of
Radiology (1996) 69, 589-593
3
 RADIOLOGY
Kainulainen et al 1999

CVID x 18, XLA x 4 3 year follow-up

CXR HRCT Disease progression (5)
Bronchiectasis 3 16
Serum IgG
Case No T=0 T=36
1 9.9 10.0
2 4.6 6.1
8 3.7 5.1
10 3.7 4.9
21 3.1 5.7
 RADIOLOGY - HRCT
RCP Specialty Specific Standards

Fit patients.CT scanning should be undertaken in

a minority of patients but usually not more than once a
year or if respiratory function tests or symptoms
deteriorate

JCIA November 2001 4

 MANAGEMENT GENERAL ISSUES

Shared Care (Immunologist/Respiratory Physician) optimal 4

Bronchodilators (reversible airflow obstruction)
Mucolytics - insufficient evidence to evaluate routine use
(Cochrane Database of Systematic Reviews. 3, 2003)
Physical therapy - insufficient evidence to support or refute usage
(Cochrane Database of Systematic Reviews. 3, 2003)
Anti-inflammatory agents
 REPLACEMENT THERAPY
Risk/benefit assessment 4
IV/Sc routes optimal 2
pulmonary infections in XLA/CVID (v untreated) 2
Optimal dosing/frequency/serum IgG level not established
Tailor route/dose/infusion frequency 3
---------------------------------------------------------------
Maintain IgG >5g/l 2
Paediatric target: mid reference range 4
IgG: >8g/l infection (v 5g/l, XLA, children) 3
9.4 g/l infection (v 6.5g/l, XLA/CVID, children/adults) 3
High v standard doses infections (no. & duration) 2
days hospitalised
serum IgG
Insidious disease progression despite adequate replacement 3
 REPLACEMENT THERAPY
High dose v low dose: secondary outcome, pulmonary function
Eijkhout et al 2001 (randomised, double-blind, multicentre, crossover, n=43)
High dose (mean trough IgG 9.4 g/l): PEFR 37.3 l/min
Standard dose (mean trough IgG 6.5 g/l): PEFR 11.4 l/min NS

Roifman & Gelfand 1988 (ramdomised, crossover, n=12)

High dose FVC & FEV1 p<0.01

Roifman et al 1987 (randomised, crossover, n=12)

Mean FEV1 & FVC high dose phase v low dose phase p<0.01

Bernatowska et al 1987 (two-dose, crossover, non-randomised, n=13)

High dose Max. expiratory flow & FEV1 NA
 ACUTE INFECTION
MICROBIOLOGY
Culture & sensitivity routinely in acute setting 3
Value unclear in chronic situation - confirm original pathogen
- ? emerging resistance
- additional pathogens

ANTIBIOTICS
Effectiveness established in exacerbations (bronchiectasis) 2
Higher doses for longer periods 4
Local treatment protocols 4
 ANTIBIOTIC PROPHYLAXIS
Chronic bronchitis - no place in routine treatment
(Cochrane Database of Systematic Reviews. 3, 2003)

Cystic fibrosis benefits - principally staphylococci

- infancy 3/6 years
- ? older children/adults
- ? > 3years treatment
(The Cochrane Library, Oxford. 2, 2003)
(Cochrane Database of Systematic Reviews. 3, 2003)

Bronchiectasis - limited meta-analysis (6 RCTs)

- marginal benefit / cautious support
(Evans et al. Thorax 2001)
 ANTIBIOTIC PROPHYLAXIS
No robust data v placebo
No substantial data v (or additional to) IVIg/SCIg (Silk et al. 1990)
? Single intervention in mild antibody deficiency
- not in more severe phenotypes / tissue damage
Papworth protocol: consider if: > 3 exacerbations / year 4
radiological / PFT deterioration
? Eradication/clean-up therapy prior to prophylaxis
- no clear evidence of benefit in antibody deficiency + structural lung damage
Development of local protocols for management of infections
(esp. with Primary Care) and initiating prophylaxis 4
 ANTIBIOTIC PROPHYLAXIS

Percentage of sputum samples growing pathogens

before and after prophylactic ciprofloxacin
70
60
50
all pathogens
40
30 H. Infl (all
%
isolates)
20
H Infl. (resistant
10 to ciprofloxacin)
0
Prior to On
ciprofloxacin ciprofloxacin
(Heelan et al., ESID 2002)
 SURGERY
Diagnostic delay > 2 years: need for surgical procedures
Adequate
treatment: lobectomy/pneumonectomy by 95%
(UK PAD Audit 1993-96) 3

Important treatment option with favourable outcomes

especially in focal bronchiectasis
(Cohen et al 1994, Mansharamani & Koziel 2003) 3
 QUESTIONS / ISSUES
HRCT in routine screening & monitoring
Radiological changes a primary therapeutic target
- Does HRCT modify our current assumptions about criteria for adequate
treatment of antibody deficiency disorders?
Correct level of Ig treatment
- arbitrary target serum level (evidence) or individualised (clinical + HRCT factors)
- single intervention universally applicable in all patients (probably not)
- higher doses: expense, complications, limited commodity
Roles of: antibiotics
anti-inflammatory agents
bronchodilators
aids to airway clearance
Role of co-factors (e.g. 1AT)
Selective IgA deficiency
 PIN GUIDELINES
Identify need for focused clinical research
Encourage debate and discussion
Reflect uncertainties in the field
Proscriptive as necessary, flexible where possible