Exhaled Breath Analysis for Cancer Diagnosis and Screening

Cancer is one of the main diseases threatening the human life and health. Early recognition is crucial to increase the survival rate of cancer patients. However, current cancer early diagnosis faces many problems. For example, current early clinical diagnostic techniques have low specificity and sensitivity but need high cost. As the progress for the medicine, the new noninvasive and fast cancer early recognition technique has come out, which is of importance to decrease the death rate. Some research results indicate that the cancer patient could emit some special gas [1], and this provides the possibility to utilize the patient’s emission gas for cancer screening, which is noninvasive, simple and sensitive. This diagnostic method has been adopted by using the trained dogs, which have the sensitive sense of smell [2]. And some research results have proven the possibility to use the dogs to realize the early diagnosis for Crimson Publishers Wings to the Research Mini Review


Data extraction and analysis
We processed and analyzed the data using the Review Manager software (Revman 5.3, provided by the Cochrane Collaboration). Random-effects models were used to calculate pooled effects. Fixed-effect models were used for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect. Dichotomous data were presented as pooled Risk Ratio (RR) with 95% confidence intervals (95% CIs), while continuous data were presented as Mean Difference (MD) with 95% CIs. We performed forest plot and funnel plot analysis to test heterogeneity and assess reporting biases. P <0.05 was considered statistically significant. Heterogeneity was assessed through the I 2 statistic, which estimates the fraction of variance that is due to heterogeneity and by Q test. The level of significance for the Q test was defined as P<0. 10.

Animal study
Ten dog olfactory detection studies in year 2006-2019 were identified, details are list as in Table 1. Two studies reported the cancer diagnosis by canine scent detection in dogs [6]. The metaanalysis results showed that there was no significant difference between the canine scent detection and biopsy-confirmed groups [RR 0.84, 95% CI 0.40 to 1.79, P=0.65, heterogeneity 2=142.11, P<0.00001, I 2 = 99%] ( Figure 1). It suggested that the accuracy of canine scent detection was the same as the pathological result as gold standard for cancer diagnosis. The analysis results conducted by the fixed-effect model are considered to show an "ideal/ typical intervention effect", and the baseline differences between the groups are considered as non-statistical heterogeneity. The heterogeneity is obvious in this meta-analysis, so the random effect model should be applied.

Clinical study
No clinical trials of gas analysis technique or product in human were identified, so no meta-analysis could be carried out. Different detection methods were summarized in Table 2. Gas analysis products for volatile organic compounds (VOCs) detection and their features, advantages and disadvantages were reported in Table 3. Currently, the main gas sensing technique includes electronic nose technique, exhaled breath condensate technique, gas chromatographic analysis, mass spectrum analysis, gas chromatograph-mass spectrum analysis, optical techniques and so on [7]. The electronic nose technique utilizes the redox reaction between the target gas and the sensor material. When the redox reaction happens, the characteristics of the sensor material would be changed, and this change would be reflected in the sensor's output signal. And through monitoring the output signal, the target gas would be quantitatively detected [8]. This kind of sensor includes the metal oxide semiconductor sensor, surface acoustic wave sensor, quartz crystal microbalance sensor and so on [9]. These sensors could be arranged in arrays and combined with pattern recognition to simulate the human's olfactory system [10]. The main advantage for exhaled breath condensate technique is the detection for the generally used protein and gene type markers in the clinical diagnosis. These markers have been used for many years, and their accuracy and stability are positive. To clinician, the acceptance of this technique is higher than other ones. The gas chromatograph-mass spectrum technique separates the detected objects and using various detection equipment to quantitatively analyze and detect the separated objects. However, the high cost and difficulty in sample making limit the practical use in the clinical diagnosis for this technique [11].

￡65 million
Lonestar VOC Analyzer is an easy to use analyzer for the detection of VOC biomarkers in clinical samples. ReCIVA® Breath Sampler is a reliable and reproducible way to capture VOC biomarkers in breath samples.

Medical diagnosis
The eNose Company have developed proprietary technology for disease screening using exhaled-breath analysis.
Combining fairly standard electronic components and advanced IT tools, small and robust electronic noses can be produced at low costs.
The Aeonose™ is the first electronic nose with the ability to avoid chemical calibration after manufacturing and employ a one-time, pre-production calibration instead. In that way, it is feasible to transfer an analysis model to a large number of eNoses without any difficulty.

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Air sense Analytics Germany Safety detection AIRSENSE centers its activity on the development and manufacturing of high-quality instruments for the fields first response, public security, aviation as well as logistics and environment.
People living in towns near plants worry about air quality. AIRSENSE offers the ability to monitor large areas and thus help you make the right decisions. Other applications in the environmental and laboratory sectors include food supervision, quality assurance and odor control.

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Electronics Sensor USA Safety detection Sensor Electronics hazardous gas detection instruments can be used to sense hundreds of different gases. From common gas types such as natural gas to exotic toxic gases like Titanium Tetrachloride.
The SEC 3000 gas detector is a unique design combining intrinsically safe and explosion proof approved standards. This toxic gas detector allows for quick and simple field installation of a calibrated sensor module into the gas detector in hazardous locations with power applied.

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Tell Spec Safety detection Tell Spec is a data company that provides predictive intelligence about food. The product combines NIR spectroscopy, bioinformatics techniques and learning algorithms to analyze consumer foods at the molecular level. Our three-part system includes the Tell spec's food sensor, a cloud-based patented analysis engine and a mobile app that work together to scan foods, identify ingredients and provide details about the food scanned.
The handheld scanner incorporates a miniature near infrared spectrometer. The internal light source focuses a beam of light through the front window into the food. Light reflected from the sample is then collected through the same window. This light is then dispersed onto a micro-mirror device and measured by an optimized detection system. This produces a digital electronic signal, known as a spectrum, characteristic of the composition of the food.

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Robo Scientific England Animal health testing The Robo Scientific family of VOC (Volatile Organic Compound) Analyzers (derived from electronic noses) contain an array of sensors that individually respond to the vapor's producing a unique response pattern for each separate type of compound or mix of compounds.
The Model 307 is a compact, rapid response and robust identification system for volatiles and gas mixtures.
The detection of the VOCs is performed using an array of the unique Robo Scientific organic semiconductor sensors. The 307 can be fitted with an array to suit your intended application and has the capability of housing between 6 and 12 individual sensors. Single VOC compounds or mixtures can be identified, after making reference measurements, by using the 'fingerprint' pattern generated from the sensors. Our sophisticated algorithms allow the instrument to be able to identify different compounds, or provides an immediate 'Good-Bad', 'Yes-No'; reaction depending upon the user's requirements and the skill of the operator.

Koniku Safety detection
Koniku is building co-processors made of biological neurons.
Nondestructive mass screening of fruits with the Koniku Kore. Fruit ripening or disease onset are not binary events. Match real world analog events with round the clock automation and nonstop volatiles sensing.

Intelligent fragrance
Aryballe develops and manufactures bio-inspired sensors enabling groundbreaking applications in digital olfaction.
NeOseTM Pro, released early 2018, the first portable and universal odor detection device developed by Aryballe.

Intelligent fragrance
The product can help everyone wake up happy, relaxed and peaceful, empowered for adventures to come.
People can choose from a wide assortment of scents, like coffee, croissants, the ocean, or even the smell of money.

Conclusion
The systematic review indicated that the analysis technique of VOCs from the human exhaled gas has the potential to be used for early cancer screening and diagnosis. The related techniques for VOCs detection are keeping developing, and the accuracy and specificity are continuously improved. However, more high-quality and large-scale randomized clinical trials are needed to confirm the effectiveness of exhaled gas analysis in cancer early diagnosis and screening.