Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects

Abstract

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FNO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CNO), airway flux (JNO), airway diffusing capacity (DNO) and airway wall content (CNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FNO at 50 ml s (FNO), 4% in JNO, 16% in CNO, 8% in DNO and 12% in CNO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

Different Relationships between FENO and COPD Characteristics in Smokers and Ex-Smokers

“…In this study, women had lower F E NO 50 values than men did, and this was the case for both smokers and ex-smokers. This differs from what was reported for the same age group in one study of healthy individuals [37], but is in line with results from other studies [40,41]. The F E NO 50 values in our study are slightly lower than values from healthy individuals, which is a known effect of smoking [10].…”

“…It has also been suggested that the antiproliferative effects of NO on airway smooth muscle might become an important clue in the quest for future strategies to prevent airway remodelling [36]. In this study, 25% of the subjects had F E NO 50 values under 8 ppb which can be compared to the lower normal limit for healthy subjects in the same age group [37]. Even though the lower level of F E NO 50 did not reach statistical significance in smokers, we did note that exsmokers with frequent exacerbations had significantly lower F E NO 50 , and when they were hospitalised for exacerbations their F E NO 50 was more likely to be on the low side.…”

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

“…These changes in F E NO seem related to somatic growth in childhood, which ends in the upper teens. The increase from middle age and up may be primarily related to structural changes in the lungs, for example loss of alveolar elastic recoil and alveolar surface area and reduced alveolar‐capillary diffusion of NO . This process probably starts earlier in women than men and to some extent explains the present findings and the findings of Jacinto et al.…”

“…Olin et al studied 2200 randomly selected healthy adults, aged 25‐75 years, and reported that sex was not independently associated with F E NO. In a recent study by Högman et al on 433 healthy subjects, age 7‐78 years, a significant sex effect on F E NO levels could be reported only for the middle age group, 20‐49 years. The mechanism of how sex affects F E NO is not fully understood, but a few hypotheses are worth mentioning.…”

“…A similar size of the sex difference has also been reported in asthmatic subjectsfor example, Al‐shamkhi et al reported that in 557 subjects with asthma from the Swedish GA2LEN study, men had 32% higher F E NO levels than women (24.0 vs 16.4 ppb). However, not all studies have been able to detect sex differences in F E NO . Olin et al studied 2200 randomly selected healthy adults, aged 25‐75 years, and reported that sex was not independently associated with F E NO.…”