1. PRIMARY ANTIBODY DEFICIENCY (PAD) & BRONCHIECTASIS (UKPIN / BTS GUIDELINES)

2. 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

3. PATHOLOGY Neutrophil proteases  Epithelial injury
(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

6. 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 ( %)

7. BRONCHIECTASIS OF UNDEFINED AETIOLOGY

8. BRONCHIECTASIS Pasteur et al
BRONCHIECTASIS Pasteur et al. Am J Respir Crit Care Med (2000) 162,
ASSOCIATION n %
Idiopathic 80 53
ABPA 11 7
PAD
Neutrophil defect 1
<1
Rheumatoid disease 4 3
Ulcerative colitis 2
Ciliary dysfunction
1.5
Young’s syndrome 5
Cystic fibrosis
Post-infectious 44 9
Aspiration/reflux 6
Other defineable

9. BRONCHIECTASIS in PAD CVID XLA 53% (Hausser et al 1983)
44% (Watts et al 1986)
18% (Hermazewski & Webster 1993)
20% (UK PAD Audit )
27% (‘chronic lung disease’) (Cunningham Rundles 1999)
58% (Garcia 2001)
43% (Busse et al 2002)
XLA
7% (Hermazewski & Webster 1993)
12% (UK PAD Audit )
20% (Quartier et al 1999)

10. 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.

12. DIAGNOSTIC DELAY Average: diagnosis - 6.3 years
treatment - additional 3.9
Diagnostic delay > 2 years:  risk of bronchiectasis
sinusitis
iron deficiency
(UK PAD Audit )
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)

13. UK PAD AUDIT
Development of bronchiectasis following diagnosis:
< >1988
77% % %

14. CHRONIC LUNG DISEASE in PAD
Damage sustained prior to active treatment
and/or
Continued inflammation despite treatment

15. 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

16. 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

17. GUIDELINES LITERATURE REVIEW DATABASES Ovid Online Collection
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 -
EBM Reviews
- Cochrane Systematic Reviews
- Cochrane Controlled Trials
- Effectiveness Reviews Abstracts
- ACP Journal Club
Allied & Complementary Medicine
Specialty Contacts

18. GUIDELINES EVIDENCE RECOMMENDATION 1 A SIGN, RCPCH, BTS 2 B 3 C 4 D
(Good Practice Points)
SIGN, RCPCH, BTS

19. DIAGNOSIS PRIMARY ANTIBODY DEFICIENCY
Humoral abnormalities are common in bronchiectasis
Respiratory Physician + Immunologist
Diagnosis of significant antibody deficiency should entail use of established and widely accepted criteria:
- 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),
- Practice parameters for the Diagnosis & Management of Immunodeficiency.
Annals of Allergy, Asthma & Immunology 1996 (76),

20. PFTs - Reversible/irreversible bronchial obstruction
- Granulomatous disease etc.
Correlate poorly with Radiology (bronchiectasis)
- Pulmonary abnormalities in patients with primary hypogammaglobulinaemia
Kainulainen et al. Jounal of Allergy & Clinical Immunology (1999) 104,
- Pulmonary manifestations of hypogammaglobulinaemia
Dukes et al. Thorax (1978) 33,
- Radiologic findings of adult primary immunodeficiency disorders: contribution of CT
Obregon et al. Chest (1994) 106,
Static volumes/flow-volume loops