Exhaled NO reference limits in a large population-based sample using the Lambda-Mu-Sigma method

Area of Science:

• Pulmonary Medicine
• Biostatistics

Background:

• Fraction of exhaled nitric oxide (FeNO) interpretation often relies on absolute values.
• Existing reference equations for FeNO may lack precision and clinical utility.
• The Lambda-Mu-Sigma (LMS) method is a statistical approach for developing age- and sex-specific reference data.

Purpose of the Study:

• To develop novel FeNO reference equations using the LMS method.
• To compare the LMS method's predictions with current absolute FeNO cut-offs.
• To enhance the clinical interpretation of FeNO measurements.

Main Methods:

• Utilized the US National Health and Nutrition Examination Surveys (2007-2012) data (n=8,340).
• Applied the LMS method within generalized additive models to natural log-transformed FeNO.
• Included sex, age, height, smoking habits, and race/ethnicity as explanatory variables.

Main Results:

• Developed a new set of FeNO reference equations based on the LMS method.
• Identified a significant proportion of individuals classified differently by LMS equations versus current recommendations.
• Observed lower predicted FeNO values compared to previous linear models.

Conclusions:

• The LMS method provides a novel and potentially more accurate model for FeNO reference values.
• This approach may improve the clinical interpretation of FeNO, aiding in the assessment of airway inflammation.
• Further validation in diverse populations with objective asthma markers is recommended.