Evolution of exhaled nitric oxide levels throughout development and aging of healthy humans

Abstract

It is not fully understood how the fraction of exhaled nitric oxide (FeNO) varies with age and gender in healthy individuals. We aim to describe the evolution of FeNO with age, giving special regard to the effect of gender, and to relate this evolution to natural changes in the respiratory tract.We studied 3081 subjects from NHANES 2007-08 and 2009-10, aged 6-80 years, with no self-reported diagnosis of asthma, chronic bronchitis or emphysema, and with normal values of blood eosinophils and C-reactive protein. The relationship of the mean values of FeNO to age, in all participants and divided by gender, was computed, and compared with changes in anatomic dead space volume and forced vital capacity. A change-point analysis technique and subsequent piecewise regression was used to detect breakpoints in the evolution of FeNO with age.Three distinct phases in the evolution of FeNO throughout the age range 6-80 years can be seen. FeNO values increase linearly between 6-14 years of age in girls and between 6-16 years of age in boys, in parallel with somatic growth. After that, FeNO levels plateau in both genders until age 45 years in females and age 59 years in males, when they start to increase linearly again. This increase continues until age 80.Our data clearly show a triphasic evolution of FeNO throughout the human age range in healthy individuals. This should be accounted for in development of reference equations for normal FeNO values.

Simultaneously elevated FeNO and blood eosinophils relate to asthma morbidity in asthmatics from NHANES 2007‐12

“…for elevated FeNO, and keeping the same cut‐off for B‐Eos (300 cells/μL) did in fact for the intermediate FeNO cut‐off lead to significant correlations between simultaneously elevated markers and most symptoms and attacks (data not shown) possibly indicating that a higher cut‐off for FeNO would be more appropriate. B‐Eos levels are also reported to vary with age, with increasing levels after 30‐40 years of age, and to be affected by smoking, where B‐Eos levels are increased in smoking subjects in a general population, but seem to decrease in asthmatic individuals who smoke . For B‐Eos, the changes in relation with asthma morbidity by increasing cut‐offs from 300 to 400 and 500 cells/μL increased slightly in this material.…”

“…Male sex, higher height and atopy relate to higher FeNO values while current smoking lowers FeNO values. FeNO values increase with age, especially during childhood and in older age . Consequently, the normal range can vary considerably and the upper limit of normal has been found to vary between 25 p.p.b.…”

The absence of serum IgE antibodies indicates non‐type 2 disease in young asthmatics

“…The percent of predicted FeNO (FeNO%) was calculated using the Malmberg algorithm, which adjusts for height in children and adolescents . In the MIDAS cohort, height should be the most significant determinant of FeNO values, according to data from a large population‐based study …”

Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III

“…Moreover, the effect of different known determinants of F E NO has not been studied with regard to gender. Specifically, the relation with age appears to be different with regard to gender, as a recent publication suggests that after a period in early adulthood with no relation between age and F E NO, an increase in F E NO with age is found at age around 45 in women and 59 years in men …”