Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review

Cameli, Paolo; Bargagli, Elena; Bergantini, Laura; d’Alessandro, Miriana; Pieroni, Maria; Fontana, Giovanni; Sestini, Piersante; Refini, Rosa Metella

doi:10.3390/ijms21176187

Cited by 18 publications

(23 citation statements)

References 99 publications

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“…The alveolar concentration of endogenous NO increases in several inflammatory interstitial lung diseases (Cameli et al, 2020), which could theoretically bias DL NO measures. However, the mean NO concentration in the gas mixtures inhaled in the present study was 63.7 ± 10 ppm, resulting in alveolar concentrations ranging from 5.4 to 21.9 ppm, thus >1,000 times the threshold considered as a marker of pulmonary alveolitis.…”

Section: Discussionmentioning

confidence: 99%

Lung diffusing capacity for nitric oxide and carbon monoxide following mild‐to‐severe COVID‐19

Barisione

Brusasco

2021

Physiol Rep

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A decreased lung diffusing capacity for carbon monoxide (DLCO) has been reported in a variable proportion of subjects over the first 3 months of recovery from severe coronavirus disease 2019 (COVID‐19). In this study, we investigated whether measurement of lung diffusing capacity for nitric oxide (DLNO) offers additional insights on the presence and mechanisms of gas transport abnormalities. In 94 subjects, recovering from mild‐to‐severe COVID‐19 pneumonia, we measured DLNO and DLCO between 10 and 266 days after each patient was tested negative for severe acute respiratory syndrome coronavirus 2. In 38 subjects, a chest computed tomography (CT) was available for semiquantitative analysis at six axial levels and automatic quantitative analysis of entire lungs. DLNO was abnormal in 57% of subjects, independent of time of lung function testing and severity of COVID‐19, whereas standard DLCO was reduced in only 20% and mostly within the first 3 months. These differences were not associated with changes of simultaneous DLNO/DLCO ratio, while DLCO/VA and DLNO/VA were within normal range or slightly decreased. DLCO but not DLNO positively correlated with recovery time and DLCO was within the normal range in about 90% of cases after 3 months, while DLNO was reduced in more than half of subjects. Both DLNO and DLCO inversely correlated with persisting CT ground glass opacities and mean lung attenuation, but these were more frequently associated with DLNO than DLCO decrease. These data show that an impairment of DLNO exceeding standard DLCO may be present during the recovery from COVID‐19, possibly due to loss of alveolar units with alveolar membrane damage, but relatively preserved capillary volume. Alterations of gas transport may be present even in subjects who had mild COVID‐19 pneumonia and no or minimal persisting CT abnormalities. Trial registry ClinicalTrials.gov PRS: No.: NCT04610554 Unique Protocol ID: SARS‐CoV‐2_DLNO 2020.

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Section: Discussionmentioning

confidence: 99%

Lung diffusing capacity for nitric oxide and carbon monoxide following mild‐to‐severe COVID‐19

Barisione

Brusasco

2021

Physiol Rep

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“…Furthermore, although no formal statistical analyses have been performed and descriptive statistics have been presented, it is notable that in the per-protocol population changes in BoPH at Day 180 were directionally similar in the THP switching group to those seen in the smoking cessation group. When compared with continued smoking, significant reductions were seen between baseline and day 180 for 8-Epi-PGF2α type III (a prostaglandin associated with systemic oxidative stress and implicated in smoking-related disease progression [36][37][38]) and white blood cell count (an inflammatory marker indicative of cardiovascular disease risk [39]), while FeNO (an indicator of airway inflammation, lung health and vascular tone [40]) levels were significantly increased. Furthermore, urinary NNAL levels were significantly reduced between baseline and day 180 and while this indicates a reduction in exposure to the tobaccospecific nitrosamine NNK, urinary NNAL levels are also considered a biomarker for lung cancer risk [30,32,33].…”

Section: Discussionmentioning

confidence: 99%

Changes in biomarkers after 180 days of tobacco heating product use: a randomised trial

et al. 2021

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The aim of this study was to investigate whether biomarkers of exposure (BoE) and potential harm (BoPH) are modified when smokers switch from smoking cigarettes to exclusive use of a tobacco heating product (THP) in an ambulatory setting. Participants in this randomised, controlled study were healthy volunteer smokers assigned either to continue smoking or switch to a THP, and a control group of smokers who abstained from cigarette smoking. Various BoE and BoPH related to oxidative stress, cardiovascular and respiratory diseases, and cancer were assessed at baseline and up to 180 days. In continuing smokers, BoE and BoPH remained stable between baseline and day 180, while THP users’ levels of most BoE reduced significantly, becoming similar to those in controls abstaining from cigarette smoking. Also at 180 days, significant changes in numerous BoPH, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, 8-epi-prostaglandin F2α type III, fractional concentration of exhaled nitric oxide and white blood cell count, were directionally consistent with lessened health impact. Our findings support the notion that the deleterious health impacts of cigarette smoking may be reduced in smokers who completely switch to using THPs.

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“…FeNO is widely accepted as a non-invasive biomarker of inflammation and oxidative stress in the lungs [ 7 ]. There are also reports of increased FeNO fraction values in interstitial lung disease with alveolar NO (CaNO) concentrations that correlate with 6-minute walking distance, oxygen saturation recovery time, total lung capacity, and forced vital capacity (FVC) [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Can FeNO be a biomarker in the post-COVID-19 patients monitoring?

Maniscalco

Ambrosino

Poto

et al. 2022

Respiratory Medicine

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The nature of the inflammatory and fibrotic processes found in patients with post-COVID-19 syndrome makes it possible to speculate that in such patients fractional exhaled nitric oxide (FeNO) may be a useful biomarker. Consequently, we set out to verify the consistency of this hypothesis. We consecutively enrolled 68 post-COVID patients after being hospitalized for persistent clinical manifestations within 2 months from disease onset and 29 healthy volunteers as control group. None of post-COVID patients had bronchial asthma or were being treated with a corticosteroid. Only 19 out of 68 post-COVID-19 patients reported a FeNO value > 25 ppb. The mean FeNO value in post-COVID-19 patients was 18.55 ppb (95% CI: 15.50 to 21.58), while in healthy subjects it was 17.46 ppb (95% CI: 15.75 to 19.17). The mean difference was not statistically significant (P = 0.053). However, the mean FeNO value of post-COVID-19 patients was higher in men than in women (20.97 ppb; 95% CI: 16.61 to 25.33 vs 14.36 ppb; 95% CI: 11.11 to 17.61) with a difference between the two sexes that was statistically significant (P = 0.016). Mean FeNO was 14.89 ppb (95% CI: 10.90 to 18.89) in patients who had been treated with systemic corticosteroids because of their COVID-19, and 20.80 ppb (95% CI: 16.56 to 25.04) in those who had not taken them, with a difference that was statistically significant (P = 0.043). The data generated in this study suggest that measurement of FeNO is not useful as a biomarker in post-COVID-19 patient. However, this hypothesis needs solid validation with additional specifically designed studies.

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Extended Exhaled Nitric Oxide Analysis in Interstitial Lung Diseases: A Systematic Review

Cited by 18 publications

References 99 publications

Lung diffusing capacity for nitric oxide and carbon monoxide following mild‐to‐severe COVID‐19

Lung diffusing capacity for nitric oxide and carbon monoxide following mild‐to‐severe COVID‐19

Changes in biomarkers after 180 days of tobacco heating product use: a randomised trial

Can FeNO be a biomarker in the post-COVID-19 patients monitoring?

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