Bronchiolitis, Bronchiolitis, Viral, Respiratory Failure, RSV Infection
Conditions
Brief summary
This study will compare the novel methods of NS and BS with the standard technique of nasophayngeal aspiration (NPA) and routine ETT suction. We shall assess the samples for diagnosis of RSV, viral load and immune responses in the airways of babies with RSV infection. We shall also assess the genetics of babies included in this study, to see if they may be vulnerable to RSV infection.
Detailed description
In conjunction with a specialist medical device manufacturing company (Hunt Developments (Midhurst, West Sussex) we have produced novel nasosorption and bronchosorption kits that have CE marking. Both nasosorption and bronchosorption methods use synthetic absorptive matrix (SAM) strips: that look and feel like blotting paper, and will be placed onto the mucosal surface. These are comfortable to use and can be used at frequent intervals over extended periods of time. This non-invasive technique is ideal for infants and children, and it is possible to obtain neat mucosal lining fluid (MLF) even from normal healthy noses. The eluates contain cytokines and chemokines at high detectable levels on multiplex immunoassay. We would like to use these SAMs to take MLF samples from the nasal and bronchial mucosal surfaces to see if these novel techniques can overcome the problems with current sampling methods. We plan to use these absorption techniques to measure RSV viral load. We also aim to look at the immune response in terms of the anti-viral interferon response (IFN-γ, IFN-λ, IFN-α2a, IP10, ITAC). In therapeutic studies in the future, it may be possible to document levels of drug (pharmacokinetics) in nasal MLF.
Interventions
DIAGNOSTIC_TESTNasal and Bronchial Sampling
Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling.
Sponsors
Pulmocide Ltd
Imperial College Healthcare NHS Trust
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Weeks to 2 Years
Healthy volunteers
Yes
Inclusion criteria
Group 1 and Group 2 Inclusion Criteria * Infants aged 2 weeks-24 months * Presentation to the Emergency Department with any upper respiratory tract infection (URTI) in the RSV season (Oct-March). OR • Documented RSV infection, admitted to the paediatric wards at St Mary's Hospital.
Exclusion criteria
* Any local or systemic factor that would influence the safety of nasal sampling. * Bilateral indwelling nasal catheters or local nasal pathology preventing access for nasal sampling. * Bleeding disorders. * The baby is taking part in another interventional study. * The parents or guardians not able to sign the informed consent from due to limited English or comprehension despite the use of independent interpreter services. * Limited life expectancy of the baby, Group 3 Inclusion criteria * Hospitalised Infants admitted to the PICU at St. Mary's Hospital, aged 2 weeks-24 months with documented RSV infection (by rapid test and/or PCR). * Infants of weight \>2kg. * On a conventional ventilator with an Endotracheal Tube (ETT) of \>3.0mmm diameter
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | Throughout symptomatic respiratory infection, up to 1 month | To determine the difference in tolerability of nasosorption compared to NPA by assessment of acceptance by infants and families. Samples were collected from participants up to twice daily throughout study involvement, as such each participant could have \>1 sampling visits. |
| Accuracy of Nasosorption for Viral Load Measurement | Throughout symptomatic respiratory infection, up to 1 month | To determine the difference in accuracy of nasosorption compared to NPA by assessment of level of viral load (measured by qPCR). |
| Accuracy of Bronchosorption for Viral Load Measurement, Compared to Tracheal Aspirate | Throughout symptomatic respiratory infection, up to 1 month | To determine the difference in accuracy of bronchosorption (BSAM) compared to tracheal aspirate (TA) by assessment of level of viral load (measured by qPCR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Response | Throughout symptomatic respiratory infection, up to 1 month | Establishing the use of nasal and bronchial sampling to measure the host immune response to RSV. We will determine cytokine and inflammatory mediator concentrations by immunoassay of eluted fluid from nasosorption and compare with NPA. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Emergency Department Babies with suspected respiratory tract infection (RTI) in the ED
Nasal and Bronchial Sampling: Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling. | 32 |
| Paediatric Wards Babies with diagnosed RSV infection admitted to paediatric wards
Nasal and Bronchial Sampling: Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling. | 51 |
| Paediatric Intensive Care Babies with diagnosed severe RSV infection in PICU requiring mechanical ventilation
Nasal and Bronchial Sampling: Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling. | 49 |
| Health Controls Babies without respiratory symptoms, attending routine outpatient appointments or undergoing elective surgical procedures
Nasal and Bronchial Sampling: Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling. | 20 |
| Controls in Paediatric Intensive Care Babies without RSV infection but requiring mechanical ventilation in PICU
Nasal and Bronchial Sampling: Nasal Absorption sampling, Bronchial sampling, Nasal Pharageal Aspirates, Blood sampling. | 0 |
| Total | 152 |
Baseline characteristics
| Characteristic | Emergency Department | Total | Health Controls | Paediatric Intensive Care | Paediatric Wards | Controls in Paediatric Intensive Care |
|---|---|---|---|---|---|---|
| Age, Continuous | 212 days | 176 days | 168 days | 168 days | 186 days | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Asian | 4 Participants | 23 Participants | 2 Participants | 5 Participants | 12 Participants | — |
| Race (NIH/OMB) Black or African American | 7 Participants | 20 Participants | 2 Participants | 5 Participants | 6 Participants | — |
| Race (NIH/OMB) More than one race | 6 Participants | 30 Participants | 6 Participants | 6 Participants | 12 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) White | 15 Participants | 79 Participants | 10 Participants | 33 Participants | 21 Participants | — |
| Region of Enrollment United Kingdom | 32 participants | 152 participants | 20 participants | 49 participants | 51 participants | — |
| Sex: Female, Male Female | 9 Participants | 53 Participants | 7 Participants | 15 Participants | 22 Participants | 0 Participants |
| Sex: Female, Male Male | 23 Participants | 99 Participants | 13 Participants | 34 Participants | 29 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 51 | 0 / 49 | 0 / 20 | 0 / 0 |
| other Total, other adverse events | 0 / 32 | 0 / 51 | 0 / 49 | 0 / 20 | 0 / 0 |
| serious Total, serious adverse events | 0 / 32 | 0 / 51 | 0 / 49 | 0 / 20 | 0 / 0 |
Outcome results
Primary
Accuracy of Bronchosorption for Viral Load Measurement, Compared to Tracheal Aspirate
To determine the difference in accuracy of bronchosorption (BSAM) compared to tracheal aspirate (TA) by assessment of level of viral load (measured by qPCR).
Time frame: Throughout symptomatic respiratory infection, up to 1 month
Population: Spearman R score correlation between RSV viral load as measured by bronchosorption and tracheal aspiration. This analysis includes all RSV+ infants independent of recruitment group as no differences in correlation between sample type were anticipated between recruitment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wards | Accuracy of Bronchosorption for Viral Load Measurement, Compared to Tracheal Aspirate | 0.45 Spearman R score |
Primary
Accuracy of Nasosorption for Viral Load Measurement
To determine the difference in accuracy of nasosorption compared to NPA by assessment of level of viral load (measured by qPCR).
Time frame: Throughout symptomatic respiratory infection, up to 1 month
Population: Spearman R score correlation between RSV viral load as measured by nasosorption and NPA. This analysis includes all RSV+ infants independent of recruitment group as no differences in correlation between sample type were anticipated between recruitment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wards | Accuracy of Nasosorption for Viral Load Measurement | 0.692 Spearman R score |
Primary
The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling
To determine the difference in tolerability of nasosorption compared to NPA by assessment of acceptance by infants and families. Samples were collected from participants up to twice daily throughout study involvement, as such each participant could have \>1 sampling visits.
Time frame: Throughout symptomatic respiratory infection, up to 1 month
Population: Parents asked at each sampling timepoint on willingness to continue with respiratory sampling, as either: 1) both nasosorption and NPA, 2) just nasosorption, 3) just NPA, 4) discontinue sampling. This analysis includes all non-sedated hospitalised participants as sedation would influence the tolerability of sampling as perceived by parents/carers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Wards | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | Nasosorption and NPA samples | 124 Sampling visits |
| Wards | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | NPA only | 0 Sampling visits |
| Wards | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | Discontinue sampling (while remaining in hospital) | 0 Sampling visits |
| Wards | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | Nasosorption only | 45 Sampling visits |
| Emergency Department | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | Nasosorption only | 4 Sampling visits |
| Emergency Department | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | Nasosorption and NPA samples | 60 Sampling visits |
| Emergency Department | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | Discontinue sampling (while remaining in hospital) | 0 Sampling visits |
| Emergency Department | The Number of Sampling Visits on Which Participants Are Willing to Undergo Nasosorption and/or NPA Sampling | NPA only | 0 Sampling visits |
Secondary
Immune Response
Establishing the use of nasal and bronchial sampling to measure the host immune response to RSV. We will determine cytokine and inflammatory mediator concentrations by immunoassay of eluted fluid from nasosorption and compare with NPA.
Time frame: Throughout symptomatic respiratory infection, up to 1 month
Population: Spearman R score correlation of Interferon-gamma levels in matched nasosorption and NPA samples from any participant. This analysis includes all RSV+ infants independent of recruitment group as no differences in correlation between sample type were anticipated between recruitment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wards | Immune Response | 0.0001 Spearman R score |