Altering the cough response after stroke

The study will be a prospective study with participants allocated to a treatment or a sham group if they meet the inclusion criteria for the study in session one. The intervention arm is ultrasonically nebulized distilled water and the comparator sham arm is physiologic saline (0.9% sodium chloride). The group allocation will be counterbalanced. The primary outcome measure is cough sensitivity. Participants are required to attend 12 sessions at the research centre. Participant checklists will be used to document session attendance. Fully trained personnel will administer all aspects of the research. Researchers conducting spirometry will be certified by the Respiratory Physiology Laboratory at Christchurch Hospital. A respiratory physician will be available for all sessions to assist with the management of any bronchoconstriction. The study will take place over a three-week period. The duration of the sessions varies through the study as detailed below. - Week 1 comprises of two sessions. Session 1 is a screening session, to ensure participants meet the criteria for the study. The session will take up to 1 hr. Session 2 consists of a cough test and will take up to 40mins. - Weeks 2 and 3 (sessions 3 - 12) are the most intensive with participants required to attend the Rose Centre for daily sessions (excluding weekends) for a two week period. Six of the sessions will take up to 1hr, and four of the sessions will take up to 1hr 30mins (total 12hrs). PROCEDURES Prior to the screening session, a phone call will occur to answer any questions the participant has and to ensure no exclusion criteria are met. Week 1 - Session 1 Participants will be required to attend the research centre and give written consent to participate in the study. Participants will complete lung function testing (see below). If their lung function is within normal limits, they will then complete a cough test (see below). This concludes the initial screening session. If they exhibit exclusionary patterns of respiratory function (see below) or cough in response to the 0.4mol/L concentration of citric acid during the cough response test, they will be excluded from further participation. They will be given a $10 MTA voucher to reimburse them for their travel expenses. Lung function testing (spirometry) Baseline spirometry will be taken in the initial session to ensure that the participant meets the inclusion criteria for the study. Spirometry will be performed on all participants by qualified clinicians certified in spirometry assessment. Age, height and weight (wearing indoor clothes without shoes) will be recorded to enable calculation of reference values. The test will be explained and they will be given instructions and a demonstration of what is required to perform the test. If their spirometry results are within the reference range the participant will be invited to continue with the study. If an obstructive pattern of respiratory function is indicated, the participant will not meet the inclusion criteria for the study. If a restrictive pattern is suggested by the results, and this has not been previously investigated, the participants GP will be informed with their consent. The GP will be required to approve their ongoing participation before they can continue with the study. Cough threshold testing Citric acid will be delivered through a mouthpiece attached to a jet nebuliser using a breath activated dosimeter and driven by an air compressor. Participants will be given instructions and a demonstration of what is required to perform the test. Nebulised citric acid will be given in ascending order from 0.4 - 3.2 mol/L (in increments of 0.4 mol/L), alongside interspersed placebo doses of physiologic saline (0.9% sodium chloride). The placebo doses will be given at identified points and this will be consistent across participants. Physiologic saline is isotonic, and therefore, is frequently used as a control condition in respiratory studies (Khan & O'Driscoll, 2004). Three inhalations of 1.2 s doses of citric acid (or saline) will be inhaled through a mouthpiece, for each trial. Tachyphylaxis is recognised to occur with repeated inhalations of citric acid (Morice et al., 2007). There will be up to a three minute break between each trial to minimize the effects of tachyphylaxis. Participants will be blinded to what they are inhaling. A cough threshold will be defined as two consecutive coughs (C2 response), on the same concentration of citric acid for two successive trials with an interspersed trial of saline. The natural cough threshold (NCT) will be identified with the instruction for participants to “inhale and exhale three times, and cough if you need to”. After each inhaled concentration of citric acid or physiologic saline trialled, participants will be asked to “rate their urge to cough” on a visual analogue scale (VAS) presented on a tablet device. One end of the scale will be marked as ‘no urge’ and the other marked ‘maximum urge’. They will be told to focus on the strength of their urge to cough, and to ignore any sensations unrelated to coughing (such as irritation or the taste of the citric acid). Week 1 (Session 2) Participants will be required to attend the research centre for a cough test. Cough threshold testing will be conducting as described previously (in session 1). Week 2 and 3 (Sessions 3 – 12) For this part of the study participants will be required to attend the research centre daily. Every session will include the stimulation protocol and lung function testing to ensure the safety of the protocol (see below). Additionally, for four of the sessions (3, 7, 8, and 12) they will have a cough threshold test to monitor changes in cough sensitivity. Cough threshold testing As described previously. Lung function testing (spirometry) Spirometry will be completed on four occasions in each session. Each test will take approximately five minutes. It will be completed once before, twice during and once after completion of the stimulation. Spirometry will be performed on all participants by researchers certified in spirometry assessment. A respiratory physician will be aware of each session, and available on the medical centre grounds at all times to address any concerns or any instances of bronchoconstriction. If a participant was to show signs of bronchoconstriction (lung inflammation) at any time during the study, they will be treated with a bronchodilator (inhaler) under the guidance of a respiratory physician until their lung function returns to normal. They will be excluded from further participation in the study. All participants will be provided with contact details of a designated respiratory physician and will be encouraged to contact the physician if they feel wheezy or short of breath in the 24 hours following the session. If required, another researcher who is not blinded to the sensory stimulation allocation will liaise with the respiratory physician and will discuss the parameters of the participants stimulation with them. Stimulation Participants will receive 3,000 high flow rate inhalations (1.6 ml/min) of either (1) distilled water or (2) physiologic saline (0.9% sodium chloride) over a period of ten sessions across ten days (i.e. 300 inhalations per session). Stimulation will not occur over the weekend, as a respiratory physician is not available. Each session is made up of 12 cycles and in each cycle the participant will receive 25 inhalations. Participants will have a ten second break after each five inhalations, and a one minute break between cycles. Spirometry will be performed four times within each session as described above.