Asthma, COPD, Cystic Fibrosis, Interstitial Lung Disease, Patients Requiring Lung Transplant
Conditions
Keywords
resistance, reactance, inflammation, lung function, respiratory function
Brief summary
Spirometry is a useful clinical tool for the assessment and monitoring of lung disease, however, it does not provide information on peripheral airways resistance. On the contrary, impulse oscillometry (IOS) may provide information not only on airway resistance (Rrs) but also on the elastic properties of the lung (Xrs). In addition, multiple breath nitrogen washout (MBNW) utilizes the exhalation of nitrogen gas from the airways to determine changes in lung ventilation and derive small airways indices (that tells us about small airways calibre). This method, like IOS, allows a precise assessment of small airways function. Even though patients with asthma may show some reduction of the caliber of the small airways these changes are more a feature of patients with COPD. The study team hypothesize that IOS and MBNW measurements may detect these differences and provide different resistance profiles for asthma and COPD. Furthermore, the study team would like to investigate the relationship between airway inflammation and small airway disease by measuring exhaled nitric oxide (NO) at multiple exhalation flow rates. This technique allows the partitioning of NO produced in the central airways from that generated more peripherally in the lung, providing valuable information on the activity of inflammation in different parts of the respiratory system. The study team hope that the combined use of IOS, MBNW and NO will identify a possible correlation between inflammation and small airway dysfunction.
Detailed description
Background The main objective of this study is to measure the damage of the small airways in lung disease exploring the silent zone with methods that have not been used before together in the same patients. Furthermore, because this is a 4 year longitudinal study, the study team will investigate the time related changes of small airway function in lung disease and normal healthy subjects. The study will also investigate the relationship between small airway resistance and inflammation.
Interventions
None listed
Sponsors
Imperial College London
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* male or female, aged between 18-85 years; * volunteers who are able to give written informed consent Patients meeting the diagnostic criteria for asthma, COPD, ILD, CF, chronic cough.
Exclusion criteria
* upper respiratory tract infection within the previous 28 days * any history or evidence of renal, cardiovascular, gastrointestinal or hepatic disease * any history and evidence of neuropsychiatric disease * treatment with antibiotics within 4 weeks prior to the study * alcohol, drug abuse or any other condition associated with poor compliance * breast feeding * pregnancy * are unable to provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 | 120 minutes | Forced expiratory volume in one second |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Calv | 120 minutes | Nitric oxide arising from the alveolar compartment. |
| AX | 120 minutes | Reactance area for whole-breath |
| R5 EX | 120 minutes | Resistance measured at 5 hertz during expiration |
| J'aw | 120 minutes | Bronchial nitric oxide flux |
| Sacin | 120 minutes | Ventilation heterogeneity within the acinar airways |
| Scond | 120 minutes | Ventilation heterogeneity within the conducting airways |
Countries
United Kingdom
Participant flow
Recruitment details
This was a single centre cross-sectional and longitudinal study involving asthmatic and chronic obstructive pulmonary disease (COPD) patients and healthy volunteers (including smokers). Subjects were between the ages of 18-85 years old, were given a patient information sheet and provided their written informed consent. Subjects were interviewed at visit 1 and a medical history was documented.
Participants by arm
| Arm | Count |
|---|---|
| Normal Subjects This group consisted of 29 never-smokers with no history of respiratory disease | 29 |
| Healthy Smokers The healthy smoking group consisted of 20 current smokers with no history of respiratory disease | 20 |
| Mild-moderate Asthma Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009). | 20 |
| Severe Asthma Asthmatics (mild, moderate and severe) were classified according to the Global Initiative for Asthma diagnostic criteria (GINA, 2009). | 23 |
| COPD (Gold Stage I - III) COPD patients (stages I - III) were classified according to the Global Initiative for Chronic Obstructive Lung Disease guidelines (GOLD, 2011). | 34 |
| Total | 126 |
Baseline characteristics
| Characteristic | Healthy Smokers | Total | COPD (Gold Stage I - III) | Severe Asthma | Mild-moderate Asthma | Normal Subjects |
|---|---|---|---|---|---|---|
| Age, Continuous | 55 years STANDARD_DEVIATION 10 | 54 years STANDARD_DEVIATION 15 | 66 years STANDARD_DEVIATION 7 | 50 years STANDARD_DEVIATION 14 | 41 years STANDARD_DEVIATION 15 | 50 years STANDARD_DEVIATION 15 |
| BMI | 23.90 kg/m^2 STANDARD_DEVIATION 4.82 | 25.5 kg/m^2 STANDARD_DEVIATION 4.8 | 25.76 kg/m^2 STANDARD_DEVIATION 4.57 | 26.89 kg/m^2 STANDARD_DEVIATION 5.64 | 24.90 kg/m^2 STANDARD_DEVIATION 4.04 | 25.63 kg/m^2 STANDARD_DEVIATION 4.8 |
| Height | 167.2 centimeters STANDARD_DEVIATION 11.3 | 168.1 centimeters STANDARD_DEVIATION 10.1 | 164.4 centimeters STANDARD_DEVIATION 8.5 | 168.7 centimeters STANDARD_DEVIATION 8.5 | 174.3 centimeters STANDARD_DEVIATION 10.1 | 168.2 centimeters STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 9 Participants | 58 Participants | 16 Participants | 6 Participants | 13 Participants | 14 Participants |
| Sex: Female, Male Male | 11 Participants | 68 Participants | 18 Participants | 17 Participants | 7 Participants | 15 Participants |
| Smoking status Current smokers | 20 participants | 30 participants | 10 participants | 0 participants | 0 participants | 0 participants |
| Smoking status Ex-smokers | 0 participants | 26 participants | 22 participants | 1 participants | 3 participants | 0 participants |
| Weight | 66.95 kilogram STANDARD_DEVIATION 15.55 | 72.2 kilogram STANDARD_DEVIATION 15.8 | 69.75 kilogram STANDARD_DEVIATION 14.04 | 76.00 kilogram STANDARD_DEVIATION 13.18 | 76.30 kilogram STANDARD_DEVIATION 17.19 | 73.05 kilogram STANDARD_DEVIATION 17.99 |
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 | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 23 | 0 / 29 | 0 / 20 | 0 / 34 |
| serious Total, serious adverse events | 0 / 20 | 0 / 23 | 0 / 29 | 0 / 20 | 0 / 34 |
Outcome results
Primary
FEV1
Forced expiratory volume in one second
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild-moderate Asthma | FEV1 | 3.03 L | Standard Deviation 0.8 |
| Severe Asthma | FEV1 | 2.32 L | Standard Deviation 0.88 |
| Normal Subjects | FEV1 | 3.18 L | Standard Deviation 0.79 |
| Healthy Smokers | FEV1 | 2.76 L | Standard Deviation 0.73 |
| COPD (Gold Stage I-III) | FEV1 | 1.67 L | Standard Deviation 0.44 |
Secondary
AX
Reactance area for whole-breath
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild-moderate Asthma | AX | 1.03 kPa/L | Standard Deviation 1.05 |
| Severe Asthma | AX | 1.88 kPa/L | Standard Deviation 2.2 |
| Normal Subjects | AX | 0.55 kPa/L | Standard Deviation 0.57 |
| Healthy Smokers | AX | 0.82 kPa/L | Standard Deviation 0.93 |
| COPD (Gold Stage I-III) | AX | 2.48 kPa/L | Standard Deviation 2.12 |
Secondary
Calv
Nitric oxide arising from the alveolar compartment.
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild-moderate Asthma | Calv | 4.3 ppb | Standard Error 3.6 |
| Severe Asthma | Calv | 3.8 ppb | Standard Error 3.2 |
| Normal Subjects | Calv | 2.9 ppb | Standard Error 1.7 |
| Healthy Smokers | Calv | 4.6 ppb | Standard Error 2.9 |
| COPD (Gold Stage I-III) | Calv | 3.7 ppb | Standard Error 2.6 |
Secondary
J'aw
Bronchial nitric oxide flux
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild-moderate Asthma | J'aw | 138.5 nl/s | Standard Deviation 85 |
| Severe Asthma | J'aw | 77.2 nl/s | Standard Deviation 62.4 |
| Normal Subjects | J'aw | 76.2 nl/s | Standard Deviation 46.1 |
| Healthy Smokers | J'aw | 35.4 nl/s | Standard Deviation 21.2 |
| COPD (Gold Stage I-III) | J'aw | 60.7 nl/s | Standard Deviation 47.6 |
Secondary
R5 EX
Resistance measured at 5 hertz during expiration
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild-moderate Asthma | R5 EX | 0.50 kPa/L/s | Standard Deviation 0.17 |
| Severe Asthma | R5 EX | 0.60 kPa/L/s | Standard Deviation 0.21 |
| Normal Subjects | R5 EX | 0.45 kPa/L/s | Standard Deviation 0.16 |
| Healthy Smokers | R5 EX | 0.50 kPa/L/s | Standard Deviation 0.25 |
| COPD (Gold Stage I-III) | R5 EX | 0.66 kPa/L/s | Standard Deviation 0.24 |
Secondary
Sacin
Ventilation heterogeneity within the acinar airways
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild-moderate Asthma | Sacin | 0.122 /L | Standard Deviation 0.094 |
| Severe Asthma | Sacin | 0.214 /L | Standard Deviation 0.194 |
| Normal Subjects | Sacin | 0.089 /L | Standard Deviation 0.051 |
| Healthy Smokers | Sacin | 0.150 /L | Standard Deviation 0.084 |
| COPD (Gold Stage I-III) | Sacin | 0.346 /L | Standard Deviation 0.139 |
Secondary
Scond
Ventilation heterogeneity within the conducting airways
Time frame: 120 minutes
Population: Not all subjects have results for this parameter which is why the total number of results will not equal the number of participants recruited.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mild-moderate Asthma | Scond | 0.041 /L | Standard Deviation 0.016 |
| Severe Asthma | Scond | 0.068 /L | Standard Deviation 0.027 |
| Normal Subjects | Scond | 0.045 /L | Standard Deviation 0.015 |
| Healthy Smokers | Scond | 0.057 /L | Standard Deviation 0.026 |
| COPD (Gold Stage I-III) | Scond | 0.057 /L | Standard Deviation 0.02 |