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