Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma (NCT02703467), a registered phase not stated study. The primary outcome is Hydrogen Sulphide in Exhaled Breath.

2. Clinical Question

3. Trial Design

The registry describes a completed study, sponsored by Imperial College London, with enrollment of 70. The recorded start date is 2015-08-01 and the primary completion date is 2016-06-30. The study title identifies its focus as exhaled hydrogen sulphide as a biomarker of airways disease in asthma.

This was not a randomized comparison. The registry describes healthy volunteers and participants diagnosed with asthma, with the asthma group spanning mild-moderate to severe disease. It does not state an allocation process. The record explicitly cautions that the arms are not a like-for-like control comparison. Group differences therefore need to be read as comparisons between the populations recruited, not as effects caused by assigning a treatment.

Participants were to attend either 2 or 4 separate visits. The registry description says measurements included hydrogen sulphide in exhaled breath and blood, exhaled nitric oxide, spirometry and asthma symptom scores. It identifies hydrogen sulphide in exhaled breath at baseline as the primary outcome, reported as a mean in parts per billion with standard error as the dispersion measure. Other listed measures include FEV1, FVC, exhaled nitric oxide and blood hydrogen sulphide level.

The registry lists five outcome measures and one analysis, but does not give the analysis method, the comparison structure for that analysis, or numerical results. The record also does not report how many participants contributed usable measurements at each visit or to each outcome. Those omissions limit assessment of the analysis and interpretation of the completed study.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Hydrogen Sulphide in Exhaled Breath, measured over At baseline visit.

The primary endpoint is the level of hydrogen sulphide in exhaled breath, measured in parts per billion at the baseline visit. It is defined as a continuous measurement, with the registry specifying the mean and standard error. A continuous endpoint retains information about the measured level rather than reducing it to categories such as high or low.

The scientific rationale in the registry is to examine whether exhaled hydrogen sulphide is related to asthma severity and could have a role in asthma management. As a general statistical point, a biomarker is useful for answering a research question only if its measured values can be interpreted in relation to relevant clinical features or outcomes. A group mean can describe the average level, while a measure of dispersion helps convey uncertainty around that average. A standard error describes uncertainty in an estimated mean; it is not the same as the spread of individual measurements.

The record does not state a clinically meaningful difference, a threshold for classifying a measurement, or a target direction of association. It also does not report the primary endpoint’s numerical results. Consequently, the endpoint definition indicates what was intended to be measured, but the registry record cannot show the levels observed or how precisely any difference or relationship was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry defines the primary outcome as a continuous measure and describes it using a mean with standard error. Continuous measurements can take a range of values. Reporting a mean gives a concise description of the group’s average, but it does not show the full distribution or reveal whether the observations are tightly clustered or widely spread. The standard error concerns the precision of the estimated mean. As a general explanation, standard error tends to become smaller when an estimate is more precise, but it should not be read as the range of values among individual participants.

Dispersion measures answer different questions. A standard deviation describes variability among individual observations, while a standard error describes uncertainty in an estimated mean. A confidence interval combines an estimate with its uncertainty to communicate a range of values reasonably compatible with the data and analysis assumptions. These are general concepts; the registry record does not report the primary mean, standard error value, standard deviation, or confidence interval. Readers therefore cannot assess the actual variability or precision of the endpoint from this record.

The central analysis question is an association between exhaled hydrogen sulphide and asthma severity. That question differs from a treatment-effect question. In a randomized treatment study, the principal comparison often concerns outcomes under assigned interventions. In this registry, the groups are healthy volunteers and people with asthma across severity levels, and the record says the comparison is not randomized or like-for-like. General statistical interpretation should therefore focus on description and association, not a causal treatment effect. The registry does not report whether severity was treated as categories, an ordered measure, or another form in the analysis.

Comparability is important when interpreting group summaries. Healthy volunteers were described as having no significant medical history and no previous asthma or other serious illnesses, being non-smokers, and having spirometry within the normal predicted range. Asthma patients were recruited from hospital asthma clinics and included a range of severity. These descriptions make clear that the groups were selected for different health characteristics. The registry record does not report adjustments for potential differences between groups, so it is not possible to determine whether any analysis accounted for them.

The study description includes repeated visits, with participants attending either 2 or 4 visits. Repeated observations from the same participant are statistically related rather than independent. As a general methodological point, an analysis of repeated measures may need to account for that within-person dependence; otherwise, uncertainty can be estimated incorrectly. However, the registry record does not state which visit data were used for each endpoint or whether repeated-measures methods were used. The primary endpoint is specifically identified at baseline, but the visit timing and analysis approach for the other measures are not fully described.

Measurement units help define what an estimate means. The primary exhaled measure is expressed in parts per billion. The registry also lists blood hydrogen sulphide, exhaled nitric oxide, FEV1 and FVC, but does not provide their numerical results or complete measurement details in the record. The list of outcomes indicates what was measured, not what values were obtained or whether a particular measure was associated with severity.

The registry notes a planning illustration based on an observed effect and describes assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These assumptions describe a planning illustration, not the trial’s own design or a reported analysis. The record does not report a sample-size justification for this study. Any sample-size figures associated with such an illustration should be understood as planning scenarios, not observed power and not proof that the study could detect a specific effect.

In general, a two-sided significance test considers departures in either direction from a null hypothesis. A significance level is a decision threshold specified for a testing procedure; it does not measure the size or importance of an association. A p-value, if reported, would describe how compatible the data are with a null model under the method’s assumptions. It would not give the probability that the null hypothesis is true. The registry record does not report a primary p-value, the null hypothesis, or enough detail to identify the statistical test used.

Over-dispersion is a general concern when the observed variability exceeds what an assumed statistical model allows. If ignored, standard errors and tests can be misleading. For this study, the record does not report a model, a dispersion assessment, or evidence of over-dispersion; it would be inappropriate to claim that this issue was present or that it was addressed. More broadly, without the analysis method and outcome values, readers cannot independently evaluate assumptions, robustness, or precision.

The registry lists five outcome measures and one analysis. It does not explain whether that analysis covered all outcomes, whether additional analyses were conducted, or how the primary endpoint was distinguished analytically from other measures. The statistical plan, including model specification, handling of covariates, and treatment of repeated observations, is not reported in the registry record. Accordingly, the endpoint definitions and general statistical principles can be described, but the specific analysis cannot be reconstructed from the record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Healthy", "Mild-moderate", "Severe")
n   <- c(20, 5, 45)
m   <- c(5, 3.2, 4.9)
sp  <- c(0.6, 1, 1.3)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Healthy  20  5.000  2.683  3.744  6.256
CARM  Mild-moderate  5  3.200  2.236  0.424  5.976
CARM  Severe  45  4.900  8.721  2.280  7.520

11. Multiplicity, Missing Data and Analysis Populations

The record lists five outcome measures and one analysis. It does not explain how the analysis related to the outcomes, identify a hierarchy among them beyond naming the primary endpoint, or report whether any adjustment for multiple testing was used. When several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. As a general statistical principle, multiplicity procedures can address that concern, but the appropriate approach depends on the planned questions and analysis. No such approach is reported in the registry record.

Missing-data handling is also not reported. The record does not state whether measurements were missing, why they might have been missing, how missing values were handled, or how many participants contributed to each analysis. It describes attendance at either 2 or 4 visits, but does not explain how incomplete visit data were treated. Without these details, readers cannot judge whether the reported or intended analyses used all available observations, restricted analysis to complete records, or applied another method.

The analysis population is not specified. The record does not say whether the primary analysis included all enrolled participants, only those with a valid baseline measurement, or another defined group. It also does not report exclusions from analysis. These omissions prevent assessment of how the analyzed participants relate to those enrolled and whether the approach to missingness or exclusions could affect interpretation.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry lists safety figures by group. For Healthy, 20 were at risk for serious events and 0 were affected; 20 were at risk for other events and 0 were affected; deaths were 0. For Mild-moderate, 5 were at risk for serious events and 0 were affected; 5 were at risk for other events and 0 were affected; deaths were 0. For Severe, 45 were at risk for serious events and 0 were affected; 45 were at risk for other events and 0 were affected; deaths were 0.

These entries mean that the registry records zero affected participants for the listed serious and other event categories in each group, and zero deaths. They do not establish that no events of any kind occurred outside the categories or reporting scope represented in the record. The record does not give event terms, observation duration for safety, or further detail on how events were collected. It lists no leading serious-event terms. Read these figures as registry safety entries, not as a comprehensive account of all possible harms.

Because the study groups were not randomized treatment arms, these counts do not provide a randomized safety comparison between interventions. The entries describe the groups as recorded and should not be interpreted as evidence about the comparative safety of a treatment.

13. What the Result Does, and Does Not, Mean

The study addresses a relevant measurement question: whether hydrogen sulphide in exhaled breath is related to asthma severity. The registry identifies a baseline mean in parts per billion as the primary outcome and describes accompanying measures, including blood hydrogen sulphide, exhaled nitric oxide, spirometry and asthma symptom scores. This makes the intended research focus clear.

What the registry record does not provide is the numerical primary result. Without the group means, uncertainty estimates, comparison or association estimate, and analysis details, readers cannot tell whether levels differed, how large any difference might have been, or how precise an estimate was. The absence of reported figures is not evidence that there was no difference or association. It means the result cannot be judged from this record.

Even a reported association would need careful interpretation. The study was not a randomized comparison, and its groups were recruited with different health characteristics. A statistical relationship between a biomarker and asthma severity would not by itself show that the biomarker causes disease severity, predicts future outcomes, or improves clinical decisions. Those are distinct questions requiring appropriate evidence.

The registry’s stated purpose includes considering a role for measurement in asthma management. This record does not report a management strategy, a comparison of decisions made with versus without the measurement, or patient outcomes resulting from its use. The endpoint description alone therefore cannot establish clinical utility.

The appropriate conclusion is narrow: the registry documents a completed study of exhaled hydrogen sulphide in healthy volunteers and people with asthma of differing severity, with baseline exhaled hydrogen sulphide as its primary measure. The numerical results and analysis needed to determine what the study found are not reported in the registry record.

14. Why This Trial Matters Statistically

Biomarker studies often begin by asking whether a measurable signal varies with a disease or its severity. This study’s stated question focuses on hydrogen sulphide in exhaled breath and asthma severity, while also recording blood hydrogen sulphide and other respiratory measures. The question is statistically important because it concerns whether a continuous measurement carries information across clinically described groups.

The design also illustrates why the comparison structure matters. A healthy group and an asthma group can provide descriptive context, but they are not interchangeable populations. The registry explicitly notes that this is not a randomized, like-for-like control comparison. That distinction helps prevent readers from interpreting group contrasts as causal effects of an intervention.

Precision is central to evaluating a biomarker result. A mean alone would not fully characterize the evidence; uncertainty and variability also matter. The registry identifies standard error as the dispersion measure for the primary endpoint, but does not report its numerical value or the endpoint results. The question may be scientifically worthwhile, yet the available record does not permit a quantitative judgment about the evidence.

The record also highlights the need for transparent analysis reporting. The study included either 2 or 4 visits, lists multiple outcomes, and does not describe missing-data handling, analysis populations, or the statistical method. These details are important for understanding how measurements were combined, how uncertainty was estimated, and how strongly conclusions can be supported.

Statistically, the most important contribution of the record is therefore its clear statement of the biomarker question and measurement framework, alongside a clear limit: numerical findings and analysis details are not reported. That distinction between a well-defined research aim and an evaluable result is essential when assessing registry evidence.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting this study from the registry is that numerical results for the primary endpoint are not reported. The record gives no group means, standard errors, estimates of association with severity, confidence intervals or p-values. It therefore does not allow readers to evaluate effect magnitude, direction or precision.

The comparison is non-randomized, and the record says the groups are not a like-for-like control comparison. Healthy volunteers and people recruited from asthma clinics differ by design. The registry does not report whether potential differences between groups were addressed analytically. Any group contrast would therefore require caution and could not be treated as a causal treatment effect.

The record does not state the statistical model, the form in which severity was analyzed, the covariates considered, or how repeated visits were incorporated. It also does not report missing-data methods, analysis populations, or participant contributions to each outcome. These omissions prevent assessment of important assumptions and the potential influence of incomplete observations.

The registry lists five outcome measures and one analysis but does not describe how multiplicity was handled or how the analysis related to each outcome. It does not report a sample-size justification for the study; the separate planning-illustration assumptions are not the study’s own design rationale. Finally, the described purpose includes a possible role in management, but the record does not report results about management decisions or patient outcomes. These limits concern what can be concluded from the registry record and do not establish what the full study may have found.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma — NCT02703467.
• Registry record last updated 2019-10-21; status last verified 2019-10.
• Results first posted 2019-10-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT02703467 is a completed study sponsored by Imperial College London, with enrollment of 70. Its recorded start date is 2015-08-01 and its primary completion date is 2016-06-30. The study concerns exhaled hydrogen sulphide as a possible biomarker in asthma and includes healthy volunteers and people with asthma across a range of severity.

The primary outcome is mean hydrogen sulphide in exhaled breath, measured in parts per billion at baseline, with standard error specified as the dispersion measure. The study description also includes blood hydrogen sulphide, exhaled nitric oxide, spirometry and asthma symptom scores, with participants attending either 2 or 4 visits. The comparison is not randomized, and the registry cautions that the groups are not like-for-like controls.

Numerical primary results, analysis methods, missing-data handling and analysis populations are not reported in the registry record. The safety entries report zero affected participants for serious and other events and zero deaths in each listed group.