Mechanisms of decrease in fractional exhaled nitric oxide during acute bronchoconstriction.
BACKGROUND
Fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (Feno50), a biomarker of airway inflammation, is affected by changes in airway caliber. Whether a lower Feno50 level during bronchoconstriction is only an artifact due to the strong flow dependence of this parameter is controversial.


METHODS
We aimed to evaluate the dynamics of airway and alveolar nitric oxide (NO) during acute bronchoconstriction induced by methacholine. Exhaled NO was measured at expiratory flows of 10, 50, 100, 150, and 250 mL/s before and after metacholine in 26 responders to methacholine and 37 nonresponders. Flow-independent parameters (airway wall NO flux, airway NO diffusing capacity, airway wall NO concentration, alveolar NO concentration) were calculated using a two-compartment model, and correction for NO axial back diffusion was applied.


RESULTS
Bronchoconstriction in responders was associated with a decrease in Feno50 (-28%, P &lt; .0001), in airway wall NO flux (-34%, P &lt; .0001), and in airway NO diffusing capacity (-15%, P &lt; .05). In contrast, alveolar NO concentration was not affected by bronchoconstriction. Postmethacholine changes in Feno50 were more strictly related to the ventilation distribution, assessed by single-breath carbon monoxide uptake, than to larger airways caliber, assessed by FEV1. When bronchoconstriction was reversed by salbutamol, airway wall NO flux and airway NO diffusing capacity returned to values comparable to those measured premethacholine.


CONCLUSIONS
The changes in airway caliber induced by noninflammatory stimuli alter NO transport in the lung. The changes in NO dynamics are limited to conductive airways and are characterized by a reduction of NO flow to luminal space.
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
Ilaria
I
Cattoni
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
Gabriella
G
Guarnieri
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
Alessandro
A
Tosetto
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
Paola
P
Mason
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
Maria C
MC
Scarpa
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy.
Marina
M
Saetta
Department of Cardiologic, Thoracic and Vascular Sciences, University of Padova, Padova, Italy. Electronic address: piero.maestrelli@unipd.it.
Piero
P
Maestrelli
D000328:Adult; D000420:Albuterol / Q000494:pharmacology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D016085:Bronchoconstrictor Agents / Q000009:adverse effects / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D045853:Exhalation / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000009:adverse effects / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000502:physiology*; D013997:Time Factors
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents; D016210:Methacholine Chloride; D009569:Nitric Oxide; D000420:Albuterol