Editorials

Exhaled Nitric Oxide in Asthma: From Diagnosis, to Monitoring, to Screening: Are We There Yet?

Asthma is a chronic inflammatory disease of the airways that is challenging to dissect into subgroups because of the heterogeneity present across the spectrum of the disease. Efforts to subclassify asthma using advanced computational methods have identified a number of different phenotypes that suggest that multiple pathobiologically driven clusters of disease exist. The main phenotypes that have been identified include (1) early-onset allergic asthma, (2) early-onset allergic moderate-to-severe remodeled asthma, (3) late-onset nonallergic eosinophilic asthma, and (4) late-onset nonallergic noneosinophilic asthma. Subgroups of these phenotypes also exist but have not been as consistently identified. Advances in our understanding of the diverse immunologic perturbations that drive airway inflammation are consistent with clinical traits associated with these phenotypes and their response to biologic therapies. This has improved the clinician's approach to characterizing asthmatic patients in the clinic. Being able to define asthma endotypes using clinical characteristics and biomarkers will move physicians toward even more personalized management of asthma and precision-based care in the future. Here we will review the most prominent phenotypes and immunologic advances that suggest these disease subtypes represent asthma endotypes.

A multichannel quartz crystal microbalance array (MQCM) with three pairs of gold electrodes was fabricated for detection of two biomarkers: acetone and nitric oxide (NO). The gold electrodes were deposited symmetrically on an AT-cut 10 MHz circular quartz plate using photolithography, sputtering, and lift-off technologies. The effect of gold layer thickness on MQCM performance was investigated and the optimized thickness was 101 nm. The simulation values of the electric parameters C₀, C_q, L_q, and R_q in the Butterworth–Van Dike equivalent circuit for the MQCM device were 97 pF, 1.3 pF, 1.05 mH, and 9.8 Ω, respectively. Simulation values were in the theoretical range, which indicated that the fabricated MQCM device had good resonance performance. Two types of nanocomposites, titanium dioxide–multiwalled carbon nanotubes and cobalt (II)phthalocyanine–silica, were synthesized as sensing materials. The sensing mechanism is based on coordination adsorption of target molecules onto the sensing material, resulting in a resonant frequency shift of modified QCM sensor. A linear range from 4.33 to 129.75 ppmv for acetone was obtained and one from 5.75 to 103.45 ppbv for NO.

Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath.

We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n = 31) and from healthy control subjects (n = 34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts.

Patients with PAH were 51.5 ± 14 years old, and 27 were women (85%). Control subjects were 38 ± 13 years old, and 22 were women (65%). Discriminant analysis in the training set identified three ion peaks (H₃O+29+, NO+56+, and O₂+98+) and the variable age that correctly classified 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classified correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9 ppb [46-77 ppb], P < .001) and was associated with right atrial pressure (ρ = 0.57, P < .001), mean pulmonary artery pressure (ρ = 0.43, P = .015), cardiac index by thermodilution (ρ = −0.39, P = .03), pulmonary vascular resistance (ρ = 0.40, P = .04), mixed venous oxygen (ρ = −0.59, P < .001), and right ventricular dilation (ρ = 0.42, P = .03).

Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease.