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  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

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 AETIOLOGY

BRONCHIECTASIS Pasteur et al BRONCHIECTASIS Pasteur et al. Am J Respir Crit Care Med (2000) 162, 1277-1284 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

BRONCHIECTASIS in PAD CVID XLA 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 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 - 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 SIGN, RCPCH, BTS 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