Lorraine Ozerovitch ( MSc, BSc, RGN ) Clinical Nurse Specialist in Respiratory Infection and Immunology

1. Lorraine Ozerovitch (MSc, BSc, RGN) Clinical Nurse Specialist in Respiratory Infection and Immunology

2. Programme • Background on Bronchiectasis and CVID • Reported quality of life outcomes in Bronchiectasis and CVID • Recent nursing research in patients with CVID-Bx compared to Id-Bx Lorraine Ozerovitch 2012 - INGID

3. Presenting history:suspicion of bronchiectasis • Unwell in childhood (bronchitis) • Period of good health • Age 30 to 40 years: persistent coughs & colds • Copious volume of purulent tenacious sputum • Lethargy or decreased exercise tolerance • Breathlessness/ Chest tightness/ Pleuritic pain Lorraine Ozerovitch 2012 - INGID

4. Assessment & Diagnosis • HRCT with CXR and sinus XR • Full PFT with reversibility • Ciliary Studies (exhaled nasal & breath NO testing/ EM) • Sputum cultures for AFB and M,C&S • Bloods (FBC, U’s&E’s, LFT’s, CRP, IgG, IgA, IgM, IgE, SpAB, Asp Rast, Asp IgG,) Lorraine Ozerovitch 2012 - INGID

5. Assessment & Diagnosis (cont.) • Serum protein electrophorectic strip • Skin prick testing • Shuttle walking Test/ Borg Breathlessness Scale • St George’s Respiratory Questionnaire • Physiotherapy review • ENT review, bronchoscopy, video-fluoroscopy, detailed immunology workup Lorraine Ozerovitch 2012 - INGID

6. Health Status • 33pts with confirmed Bx on HRCT • 25pts completed the “CAT” (Jones et al 2009) • CAT total scores correlated with worse bronchiectasis on HRCT scans: extent and severity of disease and airway wall thickness Lorraine Ozerovitch 2012 - INGID

7. What is bronchiectasis? • Chronic dilatation of peripheral airways, localised or widespread, with loss of ciliated epithelium • Occurs from destruction of muscular and elastic components of the bronchial walls • Stationary mucus acts as a breeding environment for bacteria to grow and which is the source of recurrent infections Lorraine Ozerovitch 2012 - INGID

8. Beating Cilia – in health and disease Lorraine Ozerovitch 2012 - INGID

9. Bronchiectasis - infectious agents • Common • Pseudomonas aeruginosa • Haemophilusinfluenzae • Less common • Staphylococcus aureus • Streptococcus pneumoniae • Moraxella catarrhalis • Stenotrophamonasmaltophilia • Klebsiellapneumoniae Lorraine Ozerovitch 2012 - INGID

10. A VICIOUS CYCLE OF INFECTION AND INFLAMMATION • Microbial Infection • (e.g.Haemophilusinfluenzae, Pseudomonas aeruginosa) Inflammation (Neutrophilic inflammation causes damage to the tissue through proteolytic enzymes and oxidative stress) • Impaired Lung Defences • (e.g. Antibody Deficiency, Primary Ciliary Dyskinesia, Cystic Fibrosis) Tissue Damage (To epithelial cells and the structure of the airway wall leading to increased mucus production which is poorly cleared) How does Bronchiectasis occur? • Cole (1986): The Vicious Cycle • GOAL: Halt the bacterial process which in turn will impact on the inflammatory process • The clinical course is variable Lorraine Ozerovitch 2012 - INGID

11. Prevalence • UK: 1:1000 hosp beds have a Bxpt(Sita-Lumsden and Wilson 2009) • US /NZ: 3.7-4.2: 100, 000 higher in the elderly ≥ 75yrs (Weycher et al 2005; Twiss et al 2005) • 1000 die a year, 3% increase yr on yr(Roberts and Hubbard 2010) • BTS guideline (2010) may assist clinicians’ awareness in early detection and management Lorraine Ozerovitch 2012 - INGID

12. Bronchiectasis Innate weakness in the lung’s defenses (e.g. PCD) or deficiency in the body’s ability to fight infection (e.g. CVID) Born with normal host defenses then catches a severe chest infection (e.g. tuberculosis) or experience some other insult to the airway (e.g. smoke inhalation) Acquire an excessive immune response e.g. allergic broncho-pulmonary aspergillosis (ABPA) Idiopathic – research suggest an upset in the immune response causing an exaggerated inflammatory response Causes • Modern bronchiectasis is the end result of a number of different pathologies Lorraine Ozerovitch 2012 - INGID

13. Causes of bronchiectasis Lorraine Ozerovitch 2012 - INGID

14. CVID characteristics • CVID is a heterogeneous group of conditions characterised by: Antibody deficiency, Autoimmune disorders and Granulomatous disease • Commonest cause of primary antibody deficiency (PID) • ESID criteria of CVID is “marked decrease in IgGand a reduction of a least one isotypes; IgM or IgA” • Average time between onset of symptoms and diagnosis is 7 years in the UK Lorraine Ozerovitch 2012 - INGID

15. Prevalence • Prevalence 1 in 25, 000 individuals (Parks et al 2008) • ESID database identifies 20.7% with PID has CVID (Gathmann et al 2009) • Mean age of CVID diagnosis is early 30’s • RBH bx study identified 2% had CVID, 4% had other immune deficiencies (Ozerovitch et al 2006) Lorraine Ozerovitch 2012 - INGID

16. Quality of life - Bronchiectasis • Symptoms of cough and phlegm did not impact on patients’ activity or confidence levels (Ozerovitch et al 2010) • CRP and Total WCC are systemic markers of inflammation that correlate with quality of life (Wilson et al 1998) • Dyspnoea, FEV1 and sputum production are the strongest factors of HRQL in stable bronchiectasis patients (Martinez-Garcia et al 2005) • Improved quality of life scores on follow-up compared to time of referral (Ozerovitch et al 2004) Lorraine Ozerovitch 2012 - INGID

17. Quality of life - CVID • ↑HRQoL in patients with PID on IVIG – based on self-reported measures of physical functioning (Hedderick et al 1986) • Patients reported on QoL, function and self-rated health status with IgG therapy (Gardulf et al 1993) • Studies remark of medical and clinical measures of success measures (Gardulf et al 2006) • Positive outcome in days off sick 6.1 compared to 23.3 (Eades-Perner et al 2007) Lorraine Ozerovitch 2012 - INGID

18. AIM/ First Report • To assess QoL and functional ability in adult stable patients with Bx due to CVID, compared with historical controls with idiopathic bronchiectasis (Ozerovitch et al 2004) (Note: stable patients – no acute infective event requiring additional antibiotics in the preceding month) Lorraine Ozerovitch 2012 - INGID

19. Methods • Bx confirmed on HRCT • CVID confirmed by ESID criteria • Severity of Bx noted by presence of Pseudomonas aeruginosa (Pa) • Analysis: Student t-tests Lorraine Ozerovitch 2012 - INGID

20. Assessment Tools • Spirometry • SGRQ (Wilson et al 1997; Jones 2002) • Exercise Capacity – SWT (Singh et al 1992) • The Borg Breathlessness Scale (Borg 1982) • Sputum Results (Wells et al 1993; Davies et al 2006; Loebinger et al 2009) Lorraine Ozerovitch 2012 - INGID

21. Consort diagram of study participants Lorraine Ozerovitch 2012 - INGID

22. Results Lorraine Ozerovitch 2012 - INGID

23. Quality of life and exercise tolerance results • CVID-Bx patients had better scores for all SGRQ components and better SWT distance, than Idiopathic Bx (these were clinically relevant although not statistically significant). Lorraine Ozerovitch 2012 - INGID

24. Sub-group analysis: CVID-Bx on IgGreplacement therapy *There was only a statically significant difference between the exercise tolerance scores (t-test p<0.03). Lorraine Ozerovitch 2012 - INGID

25. Microbiology results Lorraine Ozerovitch 2012 - INGID

26. Additional Results • SWT –59% walked 4-600m; total range 50-940m • Id-Bx 42% walked 4-600m; total range 0-890m • Borg scores: 59% no breathlessness pre-exertion; 64% scored between 2 to 3 (slight to mod) post exertion • Id-Bx 33% no breathlessness pre-exertion; 39% scored between 2 to 3 post exertion (Borg score≥4=39%) • Spirometry: (FEV1 64% pred) correlated negatively with Activity component only • Id-Bx no relationship Lorraine Ozerovitch 2012 - INGID

27. Discussion • Patients with CVID-Bx have clinically better health status and functional ability than demographically similar Id-Bx • SCIG therapy was found to be associated with better exercise tolerance and health status scores: however • Small no of patients studied in each group • ? Interaction of other confounding factors such as age or presence/absence co-morbidities • Little data on the utility of the Borg breathlessness scores in this specialist area. Lorraine Ozerovitch 2012 - INGID

28. Future considerations • Baseline values obtained at diagnosis or referral • Comparison group rather than historical controls • Research study used disease specific QoL tool - ?fitted to existed published work Lorraine Ozerovitch 2012 - INGID

29. Conclusion • This study provides the first report on the impact of CVID-Bx on quality of life and physical functioning using a disease specific respiratory tool • CVID-BxQoL scores were generally better than Id-Bx possibly due as a result of specific therapy (IgG replacement) in the majority of these patients Lorraine Ozerovitch 2012 - INGID

30. Acknowledgements • Patients • Dr Peter Kelleher • Dr Rob Wilson • Samantha Prigmore • Winston Banya • Dr Jill Riley Lorraine Ozerovitch 2012 - INGID