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

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 INGID

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 INGID

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 INGID

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 INGID

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 INGIDCATQuestionsQ1CoughQ2PhlegmQ3 Chest tightness Q4BreathlessnessQ5ActivitiesQ6ConfidenceQ7SleepQ8EnergyTotalScoreMean (SD) (SD)3.1(0.95)3.1(0.91)2.2(1.30)2.4(1.64)1.6(1.82)1.4(1.8)2.4(1.71)2.2(1.45)18.4(9.72)

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 INGID

Common – Pseudomonas aeruginosa – Haemophilus influenzae Less common – Staphylococcus aureus – Streptococcus pneumoniae – Moraxella catarrhalis – Stenotrophamonas maltophilia – Klebsiella pneumoniae Lorraine Ozerovitch INGID

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 INGID Microbial Infection (e.g.Haemophilus influenzae, Pseudomonas aeruginosa) 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) Inflammation (Neutrophilic inflammation causes damage to the tissue through proteolytic enzymes and oxidative stress) A VICIOUS CYCLE OF INFECTION AND INFLAMMATION

UK: 1:1000 hosp beds have a Bx pt (Sita-Lumsden and Wilson 2009) US /NZ: : 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 INGID

Modern bronchiectasis is the end result of a number of different pathologies Lorraine Ozerovitch INGID 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 Bronchiectasis

Lorraine Ozerovitch INGIDCauses N (% of study pop n ) Age (SD) No: Males (% group) Post Infection 52 (32) 49 (16) 17 (33) Idiopathic 43 (26) 51 (14) 15 (35) PCD 17 (10) 36 (13) 5 (29) ABPA 13 (8) 54 (13) 6 (46) Immune deficiency 11 (7) 47 (18) 1 (9) Ulcerative Colitis 5 (3) 48 (20) 2 (40) Young ’ s Syndrome 5 (3) 56 (5) 3 (60) Pan Bronchiolitis 4 (2) 46 (21) 3 (75) Yellow Nail Syndrome 4 (2) 55 (14) 2 (50) Mycobacterium infections 4 (2) 62 (20) 0 (0) Rheumatoid Arthritis 3 (2) 65( 4) 1 (33) Aspiration 2( 1) 67 (13) 1(50) Cystic Fibrosis 2 (1) 41 (13) 2 (100) Total (16) 58 (35) ABPA = allergic brochopulmonary aspergillosis; PCD = primary ciliary dyskinesia Shoemark et al (2007)

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 IgG and 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 INGID

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 INGID

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, FEV 1 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 INGID

↑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 INGID

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 INGID

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

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 INGID 0Nothing at all 0.5 Very, very slight (just noticeable) 1Very slight 2Slight 3Moderate 4Somewhat severe 5Severe 6 7Very severe 8 9 Very, very severe (almost maximal) 10Maximal

Lorraine Ozerovitch INGID

Biomedical and social characteristics of study participants CVID-Bx n(%) Id-Bx n(%) CVID associated bronchiectasis patients within the immunology database 340 Study participants22 (65)36 Subjects excluded12 (35)0 Male participants (%) 9 (41)12(33) Female participants (%)13 (59)24 (67) Mean age (SD) (age range) 45yrs (22.8) (17-67) 54yrs (11.30) (32-75) n of participants positive to Pa in the preceding 6 months 1 (5)13 (36) Mean FEV 1 % pred (SD)64 (26)71 (28) Participants on IgG replacement therapy (%)20 (91)0

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 INGID SGRQ Components Mean scores (SD): CVID-Bx (n=22) (Age range 17-67yrs) Mean Scores (SD): Idiopathic Bx (n=36) (Age range 32-75yrs) p: Symptoms58.3 (23.7)65.8 (22.3)0.23 Activity37.0 (27.0)45.3 (25.0)0.23 Impact27.8 (22.2)34.4 (18.1)0.22 Total Score35.8 (23.0)43.0 (18.7)0.19 SWT (m)513 (213.0)432 (157.7)0.10

*There was only a statically significant difference between the exercise tolerance scores (t-test p<0.03). Lorraine Ozerovitch INGID Total QofL Mean Score Symptom QofL Mean Score Activity QofL Mean Score Impact QofL Mean Score SWT metres Mean Score SCIG (SD) * IVIG (SD) *

Lorraine Ozerovitch INGIDPathogenCVID-Bx(n=22) CVID-Bx (baseline) Id-Bx(N=36)Id-Bx(baseline) Pseudomonas aeruginosa Steptococcus pneumoniae 0420 Haemophilus influenzae Staphlococcus Aureus 0010 Stenotrophomonas maltophilia 0011 Moroxella Catarrhalis 0100 Multi Pathogens (Hi & Strep/Staph) 0203 No growth No sputum (well)

SWT –59% walked 4-600m; total range m – 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 INGID

Patients with CVID-Bx have clinically better health status and functional ability than demographically similar Id-BxPatients 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: howeverSCIG therapy was found to be associated with better exercise tolerance and health status scores: however Small no of patients studied in each groupSmall no of patients studied in each group ? Interaction of other confounding factors such as age or presence/absence co-morbidities? 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 INGID

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 INGID

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-Bx QoL scores were generally better than Id-Bx possibly due as a result of specific therapy (IgG replacement) in the majority of these patients CVID-Bx QoL 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 INGID

Patients Dr Peter Kelleher Dr Rob Wilson Samantha Prigmore Winston Banya Dr Jill Riley Lorraine Ozerovitch INGID