Gabriella Guarnieri

Exhaled Nitric Oxide and Breath Condensate pH in Asthmatic Reactions Induced by Isocyanates

BACKGROUND We investigated the usefulness of measurements of fractional exhaled nitric oxide (FeNO) and pH of exhaled breath condensate (EBC) for monitoring airway response after specific inhalation challenges with isocyanates in sensitized subjects. METHODS Lung function (FEV(1)), FeNO, and pH in argon-deaerated EBC were measured before and at intervals up to 30 days after a specific inhalation challenge in 15 subjects with isocyanate asthma, in 24 not sensitized control subjects exposed to isocyanates, and in 3 nonasthmatic subjects with rhinitis induced by isocyanate. Induced sputum was collected before and 24 h after isocyanate exposure. RESULTS Isocyanate-induced asthmatic reactions were associated with a rise in sputum eosinophil levels at 24 h (p < 0.01), and an increase in FeNO at 24 h (p < 0.05) and 48 h (p < 0.005), whereas FeNO level did not vary with isocyanate exposure in subjects with rhinitis and in control subjects. FeNO changes at 24 h positively correlated with corresponding sputum eosinophil changes (rho = 0.66, p < 0.001). A rise in pH was observed in the afternoon samples of EBC, irrespective of the occurrence of isocyanate-induced asthmatic reactions. CONCLUSIONS We demonstrated that isocyanate-induced asthmatic reactions are associated with a consistent delayed increase in FeNO but not with the acidification of EBC.

Asthma control in elderly asthmatics. An Italian observational study

BACKGROUND The exponential increase of individuals aged >64 yrs is expected to impact the burden of asthma. We aimed to explore the level of asthma control in elderly subjects, and factors influencing it. METHODS A multicenter observational study was performed on consecutive patients >64 years old with a documented physician-diagnosis of asthma. Sixteen Italian centers were involved in this 6-month project. FINDINGS A total of 350 patients were enrolled in the study. More than one-third of elderly asthmatic patients, despite receiving GINA step 3-4 antiasthmatic therapy, had an Asthma Control Test score ≤19, with a quarter experiencing at least one severe asthma exacerbation in the previous year. Twenty-nine percent of patients (n = 101) were classified as having Asthma-COPD Overlap Syndrome (ACOS) due to the presence of chronic bronchitis and/or CO lung diffusion impairment. This subgroup of patients had lower mean Asthma Control Test scores and more exacerbations compared to the asthmatic patients (18 ± 4 compared to 20 ± 4, p < 0.01, and 43% compared to 18%, p < 0.01, respectively). Modified Medical Research Council dyspnea mMRC scores and airway obstruction, assessed on the basis of a FEV(1)/FVC ratio below the lower limit of normal, were more severe in ACOS than in asthma, without any difference in responses to salbutamol. In a multivariate analysis, the mMRC dyspnea score, FEV(1)% of predicted and the coexistence of COPD were the only variables to enter the model. INTERPRETATION Our results highlight the need to specifically evaluate the coexistence of features of COPD in elderly asthmatics, a factor that worsens asthma control.

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 < .0001), in airway wall NO flux (-34%, P < .0001), and in airway NO diffusing capacity (-15%, P < .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.

Effects of Inhalation of Thermal Water on Exhaled Breath Condensate in Chronic Obstructive Pulmonary Disease

Background: Inhalation of thermal water (TW) is traditionally used as part of the treatment of chronic obstructive pulmonary disease (COPD), but its benefit and mechanisms are controversial. We previously observed a reduced proportion of neutrophils in induced sputum after treatment with TW. Objectives: The aim of this study was to determine whether inhalation of TW in COPD patients is associated with biochemical changes of airway lining fluid, including a reduction in the neutrophil chemoattractant leukotriene B4 (LTB4). Methods: Thirteen COPD patients were randomly assigned to receive a 2-week course of TW and normal saline inhalation in a cross-over, single-blind study design. Exhaled breath condensate (EBC) was collected before and after treatments. LTB4 concentrations in EBC were determined by ELISA, and EBC pH was measured before and after argon deaeration. Results: No significant differences in LTB4 concentrations in EBC were detected with either treatment. A significant decrease in pH of non-deaerated EBC was observed after a standard course of TW (median 7.45, interquartile range 6.93–7.66, vs. median 6.99, interquartile range 6.57–7.19; p = 0.05), which disappeared after argon deaeration. Conclusions: There is no evidence that TW treatment affects LTB4 concentration in EBC. The results of EBC pH measurements suggest that TW inhalation induces an imbalance of volatile components of the buffer system in airway lining fluid.

Exhaled nitric oxide dynamics in asthmatic reactions induced by diisocyanates.

Isocyanate‐induced asthmatic reactions are associated with delayed increase in fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (FeNO50), a biomarker of airway inflammation. The time course of FeNO increase is compatible with the activation of NO synthase, but the origin of NO production in the lung is undetermined.

Cluster analysis of occupational asthma caused by isocyanates

Asthma due to isocyanates is a heterogeneous disease, which can be separated in 3 distinct phenotypes by unsupervised cluster analysis. We established that the causing agent is not sufficient to explain the heterogeneity of OA. Differences across clusters suggest that individual susceptibility and/or intensity of exposure are implicated.