PRIMARY ANTIBODY DEFICIENCY PAD

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PRIMARY ANTIBODY DEFICIENCY(PAD)BRONCHIECTASI
S(UKPIN / BTS GUIDELINES)
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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

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PATHOLOGY

• 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

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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)

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BRONCHIECTASIS OF UNDEFINED AETIOLOGY
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BRONCHIECTASISPasteur et al. Am J Respir Crit
Care Med (2000) 162, 1277-1284
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BRONCHIECTASIS in PAD

• CVID
• 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)

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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.
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DIAGNOSTIC DELAY

• Average diagnosis - 6.3 years
• treatment - additional 3.9
  
• Diagnostic delay gt 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

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UK PAD AUDIT 1993-96

• Development of bronchiectasis following
  diagnosis
• lt1980 1981-87 gt1988
• 77 70
  42

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CHRONIC LUNG DISEASE in PAD

• Damage sustained prior to active treatment
• and/or
• Continued inflammation despite treatment

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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

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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

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GUIDELINES

• 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_at_ovid
• EBM Reviews
• - Cochrane Systematic Reviews
• - Cochrane Controlled Trials
• - Effectiveness Reviews Abstracts
• - ACP Journal Club
• Allied Complementary Medicine
• Specialty Contacts

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GUIDELINES

• EVIDENCE RECOMMENDATION
• 1
  A
• 2
  B
• 3
  C
• 4
  D
• 
  
  
  
  (Good Practice Points)
• SIGN, RCPCH, BTS

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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
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• - Primary Immunodeficiency Diseases. Report
  of an IUIS Scientific Group
• Clinical Experimental Immunology 1999
  (118), Suppl 11-34
• - 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
• 
  
  
  
  

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PFTs

• - Reversible/irreversible bronchial obstruction
• - Granulomatous disease etc.
• Correlate poorly with Radiology (bronchiectasis)
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• - 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