PRIMARY ANTIBODY DEFICIENCY
(PAD)&
BRONCHIECTASIS
(UKPIN / BTS GUIDELINES)
BRONCHIECTASISBRONCHIECTASIS
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
PATHOLOGYPATHOLOGY
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 - aetiologyBRONCHIECTASIS - 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 BRONCHIECTASIS OF UNDEFINED AETIOLOGYUNDEFINED AETIOLOGY
REF. NOS. ANALYTE % age ABN.
Hilton & Doyle 1978
53 IgG/A/M 0 -
Murphy et al 1984
23 IgG/A/M, Gsub 0 -
Barker et al 1987
30 IgG/A/M, Gsub 37 Panhypoγ (9/30) IgM (2/30)
De Gracia et al 1996
65 Gsub, Hib 48 IgG2 Hib (10/19)
Hill et al 1998
89 Gsub 6 IgG4
Stead et al 2002
56 IgG/A/M, Gsub Hib, Pneum
23 IgG4 Pneum (1/29)
BRONCHIECTASISBRONCHIECTASISPasteur et al. Am J Respir Crit Care Med (2000) 162, 1277-1284
ASSOCIATION n %Idiopathic 80 53
ABPA 11 7
PAD 11 7Neutrophil 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
BRONCHIECTASIS in PADBRONCHIECTASIS in PADCVID • 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 INFECTIONSRESPIRATORY 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 DELAYDIAGNOSTIC 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 1993-96UK PAD AUDIT 1993-96
Development of bronchiectasis following diagnosis:
<1980 1981-87 >1988
77% 70% 42%
CHRONIC LUNG DISEASE in PADCHRONIC LUNG DISEASE in PAD
Damage sustained prior to active treatment
and/or
Continued inflammation despite treatment
AIMSAIMS
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
GUIDELINESGUIDELINES 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
GUIDELINESGUIDELINES
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
GUIDELINESGUIDELINES
EVIDENCE RECOMMENDATION
1 A
2 B
3 C
4 D
(Good Practice Points)
SIGN, RCPCH, BTS
DIAGNOSISDIAGNOSIS 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
PFTsPFTs
- 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