Impedance, or oscillometry, measurements of the respiratory system can generate information about the function of the respiratory system not possible with traditional spirometry. There are currently several instruments on the market using different perturbations. We have compared a new respiratory oscillometry instrument, the tremoflo, with Impulse Oscillometry (IOS). Patients with a physician's diagnosis of chronic obstructive lung disease (COPD) and healthy subjects were recruited. They underwent assessment of respiratory function with oscillometry using the IOS and tremoflo devices and the resulting impedance data from the two methods were compared. The two devices were also tested against a reference respiratory phantom with variable resistances. Whereas both devices detected impairments in the patients' lung function commensurate with small airways pathology, the tremoflo appeared to be more sensitive than the IOS. We found systematic differences between the two instruments especially for reactance measurements where the area over the reactance curve (AX) was significantly lower with the IOS compared with the tremoflo (p < 0.001). Moreover, the agreement between the two devices was reduced with increasing severity of the disease as determined with a Bland-Altman test. Testing both instruments against a respiratory phantom unit confirmed that the resistance measured by the tremoflo compares closely with the known resistance of test loads, whereas the IOS'resistance correlated with a test load of 0.19, kPa.s.L-1 at higher loads it deviated significantly from the known resistance (p < 0.0028). We conclude that the absolute values measured with the two devices may not be directly comparable and suggest that differences in the calibration procedures might account for the differences.

Background: Malignant melanoma continues to be one of the deadliest forms of skin cancer. Despite immense international efforts, it remains a major clinical challenge. To date, the golden standard for skin cancer diagnosis is through visual inspection and biopsies. UVB (280-320 nm) and IFN-γ have been proven to induce IDO-1 expression in tumor cells, increasing the ratio between tryptophan (Trp) and kynurenine (Kyn) in the tumor microenvironment. Non-invasive sampling of kyn and trp could thereby serve as an alternative for skin cancer diagnostics. 

Objective: This study aimed to investigate the clinical relevance of monitoring trp and kyn by stimulation of skin cancer development in a 3D melanoma model.

Methods: Polystyrene scaffolds were used to create 3D melanoma and melanocyte models respectively. Monolayers were used to examine keratinocytes, fibroblasts, melanoma cells, and melanocytes' response to stimuli. After treatment with UVB and IFN-g, the release of cytokines was measured with ELISA, and gene expression was analyzed with quantitative reverse transcription PCR. Secreted trp and kyn were quantified by high-performance liquid chromatography. The 3D models were then sectioned into 3 µm thick pieces for histological analysis and immunohistochemistry staining.

Results: Significantly increased gene expression of IDO-1 was seen in all monolayers, including the 3D models stimulated with IFN-g. Released IL-6 was induced after UVB exposure in the 3D models, and IL-1a was only detected in the melanocyte model. Both models showed an increase in kyn levels after stimulation with IFN-g. No induced IDO-1 gene expression could be detected in the models after UVB exposure, and no significant change in Trp/Kyn ratio was detected in those samples. 

Conclusion: Our results suggest that IFN-g induces IDO-1 gene expression in 3D models, leading to an increased trp/kyn ratio. Topical sampling of kyn and trp may be possible as an alternative non-invasive method to present diagnostics. UVB seemed to induce inflammation in the 3D models, but no significant signs of malignant transformation.