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

RADIOLOGY - HRCT - bronchial dilatation - bronchial wall thickening - classification (pathology) sensitivity (97%) > CXR 3 chromosomal radiosensitivity - plain CXR (x 3 days background) - HRCT: x 30-40 - conventional CT: x 200 ? routine baseline ? (a)symptomatic monitoring

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

RADIOLOGY Kainulainen et al 1999 3 year follow-up  CVID x 18, XLA x 4 CXR HRCT Bronchiectasis 3 16 3 year follow-up  Disease progression (5) 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

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

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 Anti-inflammatory agents

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

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

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

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) Bronchiectasis - limited meta-analysis (6 RCTs) - marginal benefit / cautious support (Evans et al. Thorax 2001)

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

ANTIBIOTIC PROPHYLAXIS (Heelan et al., ESID 2002)

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

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

PIN GUIDELINES Identify need for focused clinical research Encourage debate and discussion Reflect uncertainties in the field Proscriptive as necessary, flexible where possible