2. 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.
3. Bronchitis is a state of
increased mucus
production, with or without
adequate mucociliary
transport, that requires cough
for clearance of airway
secretions.
11. 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
12. 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
14. 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
15. 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
16. 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
17. 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
19. 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
21. 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.
22. 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).
23. Pathogenesis
• Vicious cycle:
infectious insult & impaired drainage &/or defect in host defence
• Role of positive :
genetic susceptibilty
family history
24. 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.
25. 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.
26. 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.
27. 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
28. 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).
29. Cont’d 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.
32. 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.
• Young’s disease is characterized by high lipid content of
mucus.
• Idiopathic: panbronchiolitis (responsive to macrolide) is
found mainly in Japanese and East Asia.
33. Cont’s Notes
• ABPA causes hyper immune activity.
• Atypical mycobacterial infection and
uncontrolled asthma can cause
abnormal cilia.
34. *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.
35. Clinical manifestation of cystic fibrosis
Primary
• Bronchiectasis *Nasal polyps
• Bronchiolitis, bronchitis * Cirrhosis
• Infertility * Meconium ileus
• Pancreatic insufficiency
• Pneumonia
• Salt loss
37. 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.
38. 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.
39. 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
40. 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
41. 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.
42.
43. 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.
44.
45. Notes
• The previous CT was taken for the
same patient during full
expiration, which is better than the
full inspiratory CT.
46. Cont’d investigation
• UGI Endoscopy
• Anti protease level
• Sweat test
• Genetic studies
• Rh. Factor
47. 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.
48. 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)
49. 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).
51. 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.
52. Cont’d 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.
71. HIV/AIDS Chemo-Immunosuppression
Childhood Infections M. Tb.
Innate Deficiency
Infection
Auto-Immune Inflammation Impaired Clearance
ABPM
Bronchiectasis
Altered development
72. HIV/AIDS Chemo-Immunosuppression
Childhood Infections M. Tb.
Innate Deficiency
Infection
Auto-Immune Inflammation Impaired Clearance
ABPM
Bronchiectasis
Altered development
73. Bronchiectasis
Epidemiology and Etiology
Who?
Patients - with altered immune system
- with persistent respiratory symptoms
Why?
Persistent inflammation in the respiratory system
82. 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
83. • 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
89. 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
99. 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
122. 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
123. 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
124. 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
126. Surgical Intervention
• Removal of the most involved segments
• Most common: middle and lower lobe
resecton
• Hemoptysis:
– Bronchial a. embolization
• Lung transplantation
127. 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%)
128. Chapter 14
Bronchiectasis
C
A
B
E
D
Figure 14–1. 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.
129. Three Forms of Bronchiectasis
• Varicose bronchiectasis
• Cylindrical bronchiectasis
• Saccular bronchiectasis
130. 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
132. 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).
142. 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)
150. 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
151. Normal pulmonary
artery (pearl)
Dilated bronchus
(ring)
SIGNET-RING SIGN
165. CAUSES OF ACQUIRED
BRONCHIECTASIS
• Post-infectious
• Post-obstructive
– aspirated foreign body
– slow-growing tumour
166. POST-INFECTIOUS
BRONCHIECTASIS
• Affects the part of the lung which was
involved with pneumonia
• Often diffuse as most commonly secondary to
a viral pneumonia
167. POST-OBSTRUCTIVE
BRONCHIECTASIS
• Focal or localized because only distal to the
obstructing lesion
• Dilated bronchi distal to obstruction filled
with mucus instead of air
181. 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
182. 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
186. 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 Panhypoγ (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)
187. 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
Young’s syndrome 5 3
Cystic fibrosis 4 3
Post-infectious 44 9
Aspiration/reflux 6 4
Other defineable 2 <1
188. 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)
189. 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.
190.
191. 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
192. UK PAD AUDIT 1993-96
Development of bronchiectasis following diagnosis:
<1980 1981-87 >1988
77% 70% 42%
193. CHRONIC LUNG DISEASE in PAD
Damage sustained prior to active treatment
and/or
Continued inflammation despite treatment
194. 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
197. GUIDELINES
EVIDENCE RECOMMENDATION
1 A
2 B
3 C
4 D
(Good Practice Points)
SIGN, RCPCH, BTS
198. 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
199. 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
200. 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
202. 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
203. 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
204. 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
205. 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
206.
207. 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
208. 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
209.
210. 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
211. 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)
212. 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
213. 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)
214.
215. 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
216. 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
217.
218. PIN GUIDELINES
Identify need for focused clinical research
Encourage debate and discussion
Reflect uncertainties in the field
Proscriptive as necessary, flexible where possible