Probiotics and Capsaicin Evoked Coughs
Probiotics and Capsaicin Evoked Coughs
Cough in asthma is a very common and troublesome symptom in asthma, which predicts severity
 and poor prognosis. Previous studies have shown that asthmatics have an exaggerated cough
 response to capsaicin. Currently available asthma treatment is not designed to target the
 cough reflex directly, so this presents an unmet need for patients. The treatment being
 tested in this study is the commercially available over the counter oral probiotic BioGaia®
 DSM17938. Based on clinical and pre-clinical evidence, it is hypothesized that TRPV1
 antagonism with BioGaia® DSM17938 will result in a reduction in capsaicin evoked coughs in
 patients with asthma.
Visit 1: Baseline Screening and Beginning of Treatment Period 1 Subjects will undergo
 consent, complete history, physical examination, spirometry, capsaicin cough challenge, skin
 prick testing (allergen and histamine), methacholine challenge, induced sputum and blood
 sampling. Eligible subjects will then be randomized with matched oral BioGaia DSM17938 and
 placebo and will be given for the next 4 weeks.

 Visit 2: End of Treatment Period 1 Subjects will undergo spirometry, capsaicin cough
 challenge, skin prick testing, methacholine challenge, sputum induction and blood testing.

 Washout: 28 day washout period prior to Visit 3.

 Visit 3: Beginning of Treatment Period 2 Subjects wills undergo all the same tests performed
 in visit 2. Drug/Placebo will be given for the next 28 days.

 Visit 4: End of Treatment Period 2 Subjects will undergo all the same tests performed in
 visit 2.
Inclusion Criteria:

 1. Aged ≥18

 2. Able to understand and give written informed consent

 3. Has a diagnosis of atopic asthma (based on at least one positive skin prick test and
 Methacholine PC20 ≤16 mg/ml)

 4. FEV1 (forced expiratory volume at 1 second) ≥ 70% of predicted

 5. Demonstrate a cough response to capsaicin

 Exclusion Criteria:

 1. Subjects who are in a pollen season that affects their asthma

 2. Subjects who bronchoconstrict by more than 10% at the end of the full dose capsaicin
 cough challenge (assess after visit 1)

 3. Subjects who do not display evidence of airway hyper-responsiveness (PC20>16mg/ml)
 (assess after visit 1)

 4. Symptoms of upper respiratory tract infection (URTI) in the last 1 month which have
 not resolved.

 5. Lower respiratory tract infection or pneumonia in the last 6 weeks.

 6. Current smoker or ex-smoker with ≥10 pack year smoking history and abstinence of ≤6
 months

 7. Asthma exacerbation in the previous month requiring an increase or start of an ICS
 (inhaled corticosteroids) or OCS (oral corticosteroids)

 8. Any asthma medication with the exception of infrequent (less than twice weekly)
 short-acting beta-agonist.

 9. Subjects who have changed asthma medication within the past 4 weeks prior to screening

 10. A previous asthma exacerbation requiring Intensive Care Unit (ICU) admission.

 11. Significant other primary pulmonary disorders in particularly; pulmonary embolism,
 pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis,
 emphysema or bronchiectasis.

 12. Pregnancy or breast-feeding

 13. Use of ACE (angiotensin converting enzyme) inhibitors

 14. Any centrally acting medication which in the view of the investigator could alter the
 sensitivity of the cough reflex

 15. History of psychiatric illness, drug or alcohol abuse which may interfere in the
 participation of the trial.