Multicentre trial evaluating alveolar NO fraction as a marker of asthma control and severity.

BACKGROUND: Exhaled NO can be partitioned in its bronchial and alveolar sources, and the latter may increase in the presence of recent asthmatic symptoms and in refractory asthma. The aim of this multicentre prospective study was to assess whether alveolar NO fraction and FE(NO) could be associated with the level of asthma control and severity both at the time of measurement and in the subsequent 3 months. METHODS: Asthma patients older than 10 years, nonsmokers, without recent exacerbation and under regular treatment, underwent exhaled NO measurement at multiple constant flows allowing its partition in alveolar (with correction for back-diffusion) and bronchial origins based on a two-compartment model of NO exchange; exhaled NO fraction at 50 ml/s (FE(NO,0.05)) was also recorded. On inclusion, severity was assessed using the four Global initiative for asthma (GINA) classes and control using Asthma Control Questionnaire (ACQ). Participants were followed-up for 12 weeks, control being assessed by short-ACQ on 1st, 4th, 8th and 12th week. RESULTS: Two-hundred patients [107 children and 93 adults, median age (25th; 75th percentile) 16 years (12; 38)], 165 receiving inhaled corticosteroid, were included in five centres. The two-compartment model was valid in 175/200 patients (87.5%). Alveolar NO and FE(NO,0.05) did not correlate to control on inclusion or follow-up (either with ACQ /short-ACQ values or their changes), nor was influenced by severity classes. Alveolar NO negatively correlated to MEF(25-75%) (rho = -0.22, P < 0.01). CONCLUSION: Alveolar and exhaled NO fractions are not indexes of control or severity in asthmatic children and adults under treatment.

Exhaled nitric oxide in cystic fibrosis: relationships with airway and lung vascular impairments.

A reduction of exhaled nitric oxide (NO) fraction and endothelial-mediated dysfunction have been reported in cystic fibrosis (CF). The aims of the present study were to search for relationships between flow-independent NO exchange parameters (bronchial NO flux (J'(aw,NO)) and alveolar NO concentration (C(A,NO))) and lung function tests characterising airflow limitation and pulmonary vascular bed (capillary blood volume and physiological dead space/tidal volume (V(D)/V(T)) ratio on exercise). In total, 34 patients (16 children, 18 adults) with CF, without resting pulmonary hypertension, underwent spirometry, exhaled NO measurement (multiple constant flow analytical method), gas transfer assessment (carbon monoxide and NO, allowing the calculation of capillary volume and membrane conductance) and a graded exercise test with oxygen uptake (V'(O(2))), carbon dioxide production (V'(CO(2))) and arterial blood gas evaluations. Both J'(aw,NO) and C(A,NO )correlated positively with airflow limitation. C(A,NO) correlated positively with capillary/alveolar volume. During exercise, criteria of mild pulmonary vascular disease were evidenced in some patients that participated in exercise limitation (negative correlation between physiological V(D)/V(T) and peak V'(O(2))). C(A,NO )at rest correlated positively with these parameters of wasted ventilation during exercise (physiological V(D)/V(T), minute ventilation (V'(E))/V'(CO(2)) at ventilatory threshold and V'(E)/V'(CO(2)) slope). Flow-independent exhaled NO parameters are linked to airway and early vascular diseases in patients with CF.

Diagnostic value of exhaled nitric oxide to detect interstitial lung disease in systemic sclerosis.

BACKGROUND AND AIM: Increased alveolar concentration of nitric oxide (CA(NO)) is related to the severity of interstitial lung disease (ILD) in systemic sclerosis (SSc). However, cut-off levels of CA(NO) to rule out, or to rule in, the presence of ILD in individual patients are unknown. We aimed to assess the validity of CA(NO) for the diagnosis of ILD in SSc and to determine the thresholds of CA(NO) that can be used in clinical practice to predict the likelihood of ILD in SSc. METHODS: Lung HRCT scan, PFTs and partitioned exhaled NO measurements were performed in 65 consecutive SSc patients. ILD was diagnosed on pulmonary HRCT according to the presence of ground glass or reticular opacities. Diagnostic performance of CANo for ILD diagnosis was assessed using ROC curves. RESULTS: 38 out of 65 SSc patients had ILD. CA(NO), at a cut-off level of 4.3 ppb, had a sensitivity and specificity for the diagnosis of ILD of 87% (95% CI: 77 to 99) and 59% (95% CI: 41 to 78), respectively. The same cut-off level of CA(NO) could detect impairment of gas exchange with a sensitivity and specificity of 78% (95% CI: 67 to 90) and 73% (95% CI: 46 to 99), respectively. Moreover, ILD could be ruled in (positive predictive value > 95%) when CA(NO) > or = 10.8 ppb, and ruled out C(ANO) values < or = 3.8 ppb (negative predictive value > 95%). CONCLUSION: CA(NO) could be a valid non-invasive biological marker of ILD in SSc, and be of use in clinical practice.

Individual modeling of oxygen capture by the human lungs.

It has been proposed that oxygen capture by the human lungs depends on four determinants: ventilation, cardiac output, oxygen partial pressure in the inspired air and the venous blood. Indeed, the theoretical-numerical model proposed recently by Kang et al. was able to interpret the known empirical relation between the average of the determinants and the average oxygen capture called VO2. This method is tested here at the individual level in a group of 31 subjects submitted to standard pulmonary function testing and cardiopulmonary exercise testing. For this, an inverse method is used in which individual cardiac output is predicted from the clinical test data. Comparison to the cardiac output deduced from Fick principle confirms that the dynamic model is a "microscopic" justification of the "macroscopic" Fick principle. It shows that in addition to the four determinants, two secondary determinants, namely hemoglobin concentration and Bohr effect, expressed here through P50, play significant roles.

Severity of scleroderma lung disease is related to alveolar concentration of nitric oxide.

The alveolar concentration of exhaled nitric oxide (CA,(NO)) is increased in patients with systemic sclerosis (SSc), but whether this increase is related to the severity of interstitial lung disease (ILD) in SSc has not yet been investigated. In total, 58 SSc patients prospectively underwent pulmonary function tests (PFTs), echocardiogram and fibrosis scoring on pulmonary computed tomography (CT). Patients were divided into two groups according to the presence (or not) of ILD. Measurements of CA,(NO) were assessed in all SSc patients and compared with those obtained in 19 healthy volunteers. Relationships were sought between CA,(NO) PFTs and CT scan fibrosis scores. Overall, CA,(NO) was significantly increased in SSc patients (median (range) 6.2 (3.8-9.9) ppb) as compared with controls (2.0 (1.2-3.0) ppb). Among SSc patients, CA,(NO) was significantly higher in patients with ILD compared with patients without ILD (n = 33, 7.5 (5.2-11.9) ppb versus n = 25, 4.9 (3.1-7.0) ppb, respectively). CA,(NO) was inversely related to total lung capacity (r = -0.34) and the diffusing capacity of the lung for carbon monoxide (r = -0.37) and was directly related to CT scan fibrosis scores (r = 0.36). An increased alveolar concentration of exhaled nitric oxide could, at least in part, either reflect or contribute to the severity of lung disease and could be used to noninvasively assess the extent of interstitial lung disease in systemic sclerosis.