RADIOLOGY - CXRRADIOLOGY - CXRBronchiectasis

- 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 - HRCTRADIOLOGY - 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 DISEASEUNSUSPECTED 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

RADIOLOGYRADIOLOGYKainulainen et al 1999

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 - HRCTRADIOLOGY - 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 MANAGEMENT – GENERAL ISSUES– 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

(Cochrane Database of Systematic Reviews. 3, 2003)

Anti-inflammatory agents

REPLACEMENT THERAPYREPLACEMENT 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 THERAPYREPLACEMENT THERAPYHigh 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 INFECTIONACUTE INFECTIONMICROBIOLOGY 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 PROPHYLAXISANTIBIOTIC 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) (Cochrane Database of Systematic Reviews. 3, 2003)

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

ANTIBIOTIC PROPHYLAXISANTIBIOTIC 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

(Heelan et al., ESID 2002)

Percentage of sputum samples growing pathogensbefore and after prophylactic ciprofloxacin

0

10

20

30

40

50

60

70

Prior tociprofloxacin

Onciprofloxacin

all pathogens

H. Infl (allisolates)

H Infl. (resistantto ciprofloxacin)

%

ANTIBIOTIC PROPHYLAXISANTIBIOTIC PROPHYLAXIS

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