RADIOLOGY CXR Bronchiectasis vessel crowding loss of vessel

RADIOLOGY - CXR Bronchiectasis - vessel ‘crowding’ - loss of vessel markings - tramline/ring shadows - cystic lesions/ air-fluid levels - evidence of TB Poor: l diagnostic sensitivity l monitoring of progression 3

RADIOLOGY - HRCT - bronchial dilatation - bronchial wall thickening - classification (pathology) l l 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) l l 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 l l 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 l l 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 l CVID x 18, XLA x 4 CXR Bronchiectasis 3 3 year follow-up Disease progression (5) l HRCT 16 Case No 1 2 8 10 21 Serum Ig. G T=0 T=36 9. 9 10. 0 4. 6 6. 1 3. 7 5. 1 3. 7 4. 9 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 l l l Shared Care (Immunologist/Respiratory Physician) optimal Bronchodilators (reversible airflow obstruction) Mucolytics - insufficient evidence to evaluate routine use (Cochrane Database of Systematic Reviews. 3, 2003) l Physical therapy - insufficient evidence to support or refute usage (Cochrane Database of Systematic Reviews. 3, 2003) l Anti-inflammatory agents 4

REPLACEMENT THERAPY l Risk/benefit assessment l IV/Sc routes optimal l pulmonary infections in XLA/CVID (v untreated) Optimal dosing/frequency/serum Ig. G level not established l Tailor route/dose/infusion frequency l 4 2 2 3 -------------------------------l l l Maintain Ig. G >5 g/l Paediatric target: mid reference range Ig. G: >8 g/l infection (v 5 g/l, XLA, children) 9. 4 g/l infection (v 6. 5 g/l, XLA/CVID, children/adults) High v standard doses infections (no. & duration) days hospitalised serum Ig. G Insidious disease progression despite ‘adequate’ replacement 2 4 3 3 2 3

REPLACEMENT THERAPY High dose v low dose: secondary outcome, pulmonary function l l Eijkhout et al 2001 (randomised, double-blind, multicentre, crossover, n=43) High dose (mean trough Ig. G 9. 4 g/l): PEFR 37. 3 l/min Standard dose (mean trough Ig. G 6. 5 g/l): PEFR 11. 4 l/min NS Roifman & Gelfand 1988 (ramdomised, crossover, n=12) High dose FVC & FEV 1 p<0. 01 Roifman et al 1987 (randomised, crossover, n=12) Mean FEV 1 & 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 & FEV 1 NA

ACUTE INFECTION MICROBIOLOGY l Culture & sensitivity routinely in acute setting l Value unclear in chronic situation - confirm original pathogen - ? emerging resistance - additional pathogens ANTIBIOTICS l Effectiveness established in exacerbations (bronchiectasis) l Higher doses for longer periods l Local treatment protocols 3 2 4 4

ANTIBIOTIC PROPHYLAXIS l Chronic bronchitis - no place in routine treatment (Cochrane Database of Systematic Reviews. 3, 2003) l Cystic fibrosis benefits - principally staphylococci - infancy 3/6 years - ? older children/adults - ? > 3 years treatment (The Cochrane Library, Oxford. 2, 2003) (Cochrane Database of Systematic Reviews. 3, 2003) • Bronchiectasis - limited meta-analysis (6 RCTs) - marginal benefit / cautious support (Evans et al. Thorax 2001)

ANTIBIOTIC PROPHYLAXIS l l l 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 l Papworth protocol: consider if: > 3 exacerbations / year 4 radiological / PFT deterioration l ? Eradication/clean-up therapy prior to prophylaxis - no clear evidence of benefit in antibody deficiency + structural lung damage l Development of local protocols for management of infections (esp. with Primary Care) and initiating prophylaxis 4

ANTIBIOTIC PROPHYLAXIS (Heelan et al. , ESID 2002)

SURGERY l Diagnostic delay > 2 years: need for surgical procedures A dequate treatment: lobectomy/pneumonectomy by 95% (UK PAD Audit 1993 -96) l 3 Important treatment option with favourable outcomes especially in focal bronchiectasis (Cohen et al 1994, Mansharamani & Koziel 2003) 3

QUESTIONS / ISSUES l l 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? l 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 l Roles of: antibiotics anti-inflammatory agents bronchodilators aids to airway clearance l l Role of co-factors (e. g. 1 AT) Selective Ig. A deficiency

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