Experimental Human Pneumococcal Carriage: Asthma and immune functio

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 62

Inclusion Criteria

1. World Health Organisation performance status 0 (able to carry out all normal activity without restriction) or 1 (restricted in strenuous activity but ambulatory and able to carry out light work)
2. Fluent spoken English - to ensure a comprehensive understanding of the research project and their proposed involvement
3. Access to their own mobile telephone (safety and timely communication)
4. Capacity to give informed consent
5. Adults aged 18-50 years, with a physician diagnosis of asthma; BTS treatment step 2 and 3 (see Appendix 1)
6. No exacerbations requiring antibiotics or oral steroids within the last 28 days
7. Spirometry: Forced Expiratory Volume in one second >70% predicted

Exclusion Criteria

1. Close physical contact with at-risk individuals (children under 5yrs, immunosuppressed adults) - minimise risk of pneumococcal transmission
2. History of drug or alcohol abuse (frequently drinking over the recommended alcohol intake limit: men and women should not regularly drink more than 14 units of alcohol per week. – minimise risk of pneumococcal disease
3. Smoking any cigarettes currently or within the last six months - minimise risk of pneumococcal disease
4. Ex-smoker with a significant smoking history (>10 pack years) – minimise risk of pneumococcal disease (For loose tobacco: ounces per week × 2/7 × number of years smoked ?=? pack years(22))
5. Taking regular daily medications that may affect the immune system e.g. oral steroids, steroid nasal spray, antibiotics, and disease-modifying anti-rheumatoid drugs.
6. Any acute illness (new symptoms within preceding 14 days which are unexplained by the known past medical history)
7. Having received any antibiotics, oral steroids or nasal steroid spray in the preceding 28 days
8. More than 1 asthma exacerbation in the last twelve months (Asthma exacerbation defined as an acute episode of progressive worsening of symptoms of asthma, including shortness of breath, wheezing, cough, and chest tightness, or a decline in objective measure such as peak expiratory flow rates of more than 30 percent requiring treatment with oral corticosteroids for a period of 3 days or more)
9. Taking medication that affects blood clotting e.g. aspirin, clopidogrel, warfarin or other oral or injectable anticoagulants
10. History of culture-proven pneumococcal disease
11. Allergy to penicillin/amoxicillin
12. Currently involved in another clinical trial unless observational or in follow-up (non-interventional) phase.
13. Have been involved in a clinical trial involving EHPC and bacterial inoculation in the past three years
14. Significant cardiorespiratory disease (excluding stable hypertension, and asthma at treatment step 2 and 3)
15. Disease associated with altered immunity, including diabetes, alcohol abuse, malignancy, rheumatological conditions
16. Pregnancy
17. Taking any medications except those on the allowed list”. The allowed medications” list encompasses mediations which will not cause significant alteration to our measures of immune function, and which are used in the treatment of co-morbidities. These are: statins; anti hypertensives in stable hypertension; antidepressants; bisphosphonates; treatment for benign prostatic hyperplasia; hormone replacement therapy; vitamin supplements (including multivitamins, iron); anti-acid medications; nicotine replacement therapy (NRT), inhaled steroids upto 800 micrograms BDP equivalent per day, inhaled beta 2 agonists and leukotriene receptor antagonist.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Detection of S. pneumoniae by classical bacteria culture methods from one or more nasal wash samples collected following initial pneumococcal challenge at days 2, 7, 9, 14, 22 and 29.

Secondary Outcome Measures

Name	Time	Method
1. Duration and density of pneumococcal carriage in people with asthma is measured using microbial culture at days 2, 7, 9, 14, 22 and 29.<br>2. Rates of experimental human pneumococcal carriage among people with asthma at BTS treatment step 2 and 3 is measured using microbial culture at days 2, 7, 9, 14, 22 and 29.<br>3. Protective effect of initial carriage on the reacquisition of carriage after a second inoculation is measured using microbial culture at days 2, 7, 9, 14, 22 and 29