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Can dogs smell lung cancer? First study using exhaled breath and urine screening in unselected patients with suspected lung cancer

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Abstract

Background: On the basis of our own experience and literature search, we hypothesised that a canine olfactory test may be useful for detecting lung cancer in an unselected population of patients suspected to have lung cancer. Material and methods: We conducted a prospective study of 93 patients consecutively admitted to hospital with suspected lung cancer. Exhaled breath and urine were sampled before the patients underwent bronchoscopy. The canine olfactory test was performed in a double-blinded manner. Sensitivity and specificity were outcome measures. Results: With 99% sensitivity, the olfactory test demonstrated that dogs have the ability to distinguish cancer patients from healthy individuals. With an intensified training procedure, the exhaled breath and urine tests showed sensitivity rates of 56-76% and specificity rates of 8.3-33.3%, respectively, in our heterogeneous study population. Conclusion: Although the olfactory test appears to be a promising tool for the detection of cancer, the main challenge is to determine whether the test can sufficiently discriminate between patients at risk, patients with benign disease, and patients with malignant disease. We need to gain a deeper understanding of this test and further refine it before applying it as a screening tool for lung cancer in clinical settings.

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... Early diagnosis of the tumour is therefore very crucial for better treatment outcomes and increased patient survival. 1,11,15 The use of CT as a diagnostic tool has shown a 20% reduction in mortality. 11,2,7 However, these techniques have their limitations. ...
... 22 Dogs have always been used in rescue and police services (to detect drugs, explosives, identify people). 1,22 Tumour detection using the dog's sense of smell appeared as early as 1989 when the first case of a woman diagnosed with melanoma by her dog was mentioned. 22,25 More than 30 years have passed since then, and variety of study results are observed across research teams. ...
... None of the monitored studies indicated which material produced the more valid results. 1,11,13,15,7 Our centre use serum samples, but we also used breath samples in the experiment. The experiments were not paired, ie. ...
Article
Background Lung cancer is one of the most often diagnosed tumours in the world with the highest mortality. A major problem and reason for the high mortality from lung cancer is its diagnosis in the late stages. The main goal of preventing lung cancer deaths is early detection in the early stages and accurate diagnosis, which must be followed by targeted treatment. Nevertheless, even top diagnostic techniques do not have the same accuracy and sensitivity as a dog’s sense of smell. Methods The study aims to present the results of olfactometric detection of lung cancer using the smell of dogs in unblinded, single-blinded and double-blinded studies. 115 serum samples or breath from patients with lung cancer and 101 samples from healthy people were used for the training. The group consisted of women and men of Indo-European origin, mostly from the Moravian-Silesian region in Czech Republic. Two dogs were selected for the study. Results In the case of tumor detection in the form of unblinded tests, Bugs had a sensitivity of 91% and a specificity of 92%. Boolomo had a sensitivity of 89% and a specificity of 81%. For single-blinded tests, Bugs had a sensitivity of 71%. The sensitivity of Boolomo was set at 90%. After meeting the sensitivity limit of 70%, dogs were included in the double-blinded studies. The highest accuracy was set at 68% for Bugs, 83% for Boolomo. Conclusion When a tumour is diagnosed in the late stages, it is a great burden on both the health and economic systems of the state. Unfortunately, there is still no suitable screening test to detect the tumour at an early stage, so any other method of detection seems desirable. Trained dogs are used in many fields, why not also in medicine and the diagnosis of tumours?
... Including single cancer samples among a number of control samples in a blinded setting sensitivity was 71-99% and specificity 91-99%, usually obtained as a 'corporate decision' of all participating dogs [11][12][13]. When dogs were confronted with a situation of variable numbers of cancer samples (0-6 cancer samples in each trial) sensitivity and specificity decreased to 56 and 34%, respectively [14,15]. Different approaches have been followed concerning sample carrier materials and collection. ...
... Different approaches have been followed concerning sample carrier materials and collection. While some studies used tumor tissue, urine or stool samples, most of the other studies worked with breath samples, collected with different carrier materials, such as sampling tubes filled with different fleeces or charcoal or sterile exhalation filters [11][12][13][14][15][16][17]. Moreover, dogs have been trainedwhile several studies have trained household dogs with only basic obedience training, other studies used dogs with workingexperience like scent tracking or search and rescue dogs. ...
... The dogs had to identify one cancer breath sample within several control samples. In contrast, two other studies showed worse results, sensitivity being 45-76% and specificity 8-53%, if dogs were confronted with a real-life screening-like situation and when varying the number of LC samples (between 0 and 5) in a double-blind setting [14,15]. In our methodological part of the study sensitivity was 36-50% and specificity 60-69%, while in the main study sensitivity was 56% and specificity 83%, underlining the importance of the experimental settings. ...
Article
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Background: It has been reported that canine scent tests offer the possibility to screen for cancer. Assuming that breath samples can be collected with carrier materials, we tested the practicability of different carrier materials to be presented to dogs and validated and compared results with an electronic nose (eNose). Moreover, we hypothesized that cancer detection ability of dogs differs according to their working experience. Methods: In a methodological approach, two dog teams participated, one using experienced working dogs and the other ordinary household dogs to find the most qualified dogs and training method. To find best carrier material for breath sampling we compared charcoal containing glass tubes and fleece masks. In a second validating part, experienced working dogs were trained with improved training strategies. For breath sampling, two different, previously successfully tested fleece-based carrier materials were used: one was used with the dog team and both materials were compared with eNose. Results: In the methodological approach, it turned out that the charcoal-based sampling strategy qualified not sufficiently for VOC-detection. Moreover, we could determine that using experienced working dogs provided several advantages. Overall results of dogs in the validating part regarding specificity were 83%, regarding sensitivity 56%, but with great variability among dogs. Using eNose for breath analysis collected with both fleece carrier materials, specificity was 97% and sensitivity 89–100%. Conclusion: Our data confirmed that the diagnostic accuracy of dogs depended on the type of dog training and on the carrier materials. A comparison of breath samples analysis with an eNose achieved better results for both, sensitivity and specificity than for dogs. The use of fleece masks or fleeces in glass tubes as a sampling material can be recommended as successful VOC carriers, encouraging their use for clinical screenings.
... Rudnicka et al. (2014) pointed out, however, that when examining each dogs' performance individually, it was apparent that one dog detected lung cancer better than the other. Finally, Amundsen et al. (2014) attempted to determine whether dogs could distinguish between malignant and benign conditions. To begin, Amundsen et al. (2014) trained dogs to identify lung cancer by presenting the dogs with cancerous tissue samples and breath samples from healthy controls; a task that the dogs completed with a high degree of sensitivity and specificity. ...
... Finally, Amundsen et al. (2014) attempted to determine whether dogs could distinguish between malignant and benign conditions. To begin, Amundsen et al. (2014) trained dogs to identify lung cancer by presenting the dogs with cancerous tissue samples and breath samples from healthy controls; a task that the dogs completed with a high degree of sensitivity and specificity. However, when Amundsen et al. (2014) subsequently presented the dogs with a series of heterogenous breath samples that were obtained from individuals with either malignant or benign conditions (as would be expected in a real world applied setting), the dogs' were only able to detect the malignant conditions with overall sensitivity and specificity of 56% and 33% respectively; a more challenging task than previous studies, and the results were much less promising. ...
... To begin, Amundsen et al. (2014) trained dogs to identify lung cancer by presenting the dogs with cancerous tissue samples and breath samples from healthy controls; a task that the dogs completed with a high degree of sensitivity and specificity. However, when Amundsen et al. (2014) subsequently presented the dogs with a series of heterogenous breath samples that were obtained from individuals with either malignant or benign conditions (as would be expected in a real world applied setting), the dogs' were only able to detect the malignant conditions with overall sensitivity and specificity of 56% and 33% respectively; a more challenging task than previous studies, and the results were much less promising. As evidenced by the findings of the studies discussed here, dogs' ability to detect lung cancer is uncertain. ...
Article
In empirical tests of biomedical detection dogs, exhaled breath samples are often used because breath contains volatile organic compounds that can signal metabolic states, infection, or disease. However, in studies that present dogs with breath samples, results show a notable degree of variability both between and within studies. Differing protocols for the collection and storage of exhaled breath samples may contribute to this observed variability. The goal of the current study was therefore to test whether there was a difference in the detectability of breath samples collected using silicone-coated versus uncoated cotton balls. This was tested in two experiments. In the first experiment, breath samples were prepared using both silicone-coated and uncoated cotton balls, which were then left exposed to the surrounding air. Four dogs' detection of the samples was tested using a cued, three alternative forced choice (3AFC) procedure at regular intervals up to two hours after the samples were prepared. The results of Experiment 1 showed that the dogs' performance was above chance and there was no significant difference in the dogs' detection of the breath samples across conditions. In the second experiment, a series of breath samples were prepared and stored for one, two, three, and four week periods. The same four dogs' ability to detect the breath samples was tested each week using the same MTS/3AFC procedure. The results of Experiment 2 showed that when silicone-coated cotton balls were used, all four dogs could detect the breath samples at above chance levels after the samples were stored for three weeks, and two dogs could detect the samples that were stored for four weeks. When the dogs were tested on their ability to detect the breath samples prepared using uncoated cotton, two dogs' performance fell to below chance levels at one week of storage time, while the other two dogs could detect the breath samples at above chance levels after the samples were stored for four weeks. Taken together, the results of the two experiments illustrate that silicone-coated cotton balls do not improve detectability of breath samples within two hours, but can greatly improve the detectability of breath samples stored over longer periods of time. Since the use of silicone-coated cotton balls only improved the detectability of the breath samples for two of the four dogs, these results highlight the importance of examining individual differences in dogs' performance. Furthermore, we argue that, given the inherent differences in olfactory ability across dogs, widespread use of silicone-coated cotton balls for the collection of breath samples would increase the pool of testable dogs for biomedical detection studies and would decrease the degree of variability both within and between studies.
... For instance Ehmann et al (2012) investigating lung cancer reported sensitivity of 0.71 and specificity of 0.93. Two years later Amundson et al (2014) also investigating lung cancer reported sensitivities ranging from 0.62 to 0.65 and specificities from 0.08 to 0.16. Moreover there are inconsistencies in the methodologies used across the field (Moser and McCulloch, 2010). ...
... A number of the reviewed studies do not report the duration of training (such as Ehmann et al (2012) and McCulloch et al (2006)). Training is often continued throughout the study duration as in Amundson et al, 2014 who maintained two training sessions per week, following low initial accuracy this training increased to four sessions per week. The test procedure usually takes place in a bare, familiar room (fewer distractions) with/without an observer present. ...
... This study attempts to display canine odour recognition as a robust method and thus contains no participant restrictions such as diet or smoking status. More recently Amundson et al. (2014) tested the olfactory ability of 4 canines a Belgian Shepard, Boarder collie, Hard hair dachshund, and Rottweiler to detect lung cancer using exhaled breath and urine. Samples were taken from 93 patients admitted to hospital with suspected lung cancer; none of the participants were healthy, 59 were diagnosed with lung cancer. ...
Article
Numerous studies have attempted to demonstrate the olfactory ability of canines to detect several common cancer types from human bodily fluids, breath and tissue. Canines have been reported to detect bladder cancer (sensitivity of 0.63-0.73 and specificity of 0.64-0.92) and prostate cancer (sensitivity of 0.91-0.99 and specificity of 0.91-0.97) from urine; breast cancer (sensitivity of 0.88 and specificity of 0.98) and lung cancer (sensitivity 0.56-0.99 and specificity of 8.30-0.99) on breath and colorectal cancer from stools (sensitivity of 0.91-0.97 and specificity of 0.97-0.99). The quoted figures of sensitivity and specificity across differing studies demonstrate that in many cases results are variable from study to study; this raises questions about the reproducibility of methodology and study design which we have identified herein. Furthermore in some studies the controls used have resulted in differentiation of samples which are of limited use for clinical diagnosis. These studies provide some evidence that cancer gives rise to different volatile organic compounds (VOCs) compared to healthy samples. Whilst canine detection may be unsuitable for clinical implementation they can, at least, provide inspiration for more traditional laboratory investigations.
... Certain foods, drinks, or drugs may interfere with the odor of disease related compounds (Amundsen et al., 2014;Willis et al., 2004). No need for surveillance methods processes rely on the collection of diagnostic samples from individuals, transportation of samples to a laboratory, and laboratory testing (T. ...
... Non-invasive diagnostic method . The dog is a living creature that gets hurt and may be influenced by intercurrent infections or allergies, which may reduce the quality of the olfactorial test conditions (Amundsen et al., 2014). Immediate identification of infected people. ...
... C. . On the other hand the olfactory test depends on various factors including environmental conditions, such as relative humidity and also intercurrent infections or allergies, given that the dog is a living creature may be influenced by these condition (Amundsen et al., 2014;Jenkins et al., 2018). ...
... In addition, when a new set of samples was tested for the first time (first trial), the detection sensitivity fell further (68% and 37% at 50% and 20% probability levels, respectively) although it was still significantly better than by chance alone. In a recent study, Amundsen et al. (2014) used the olfactory test in double-blind conditions to detect lung cancer in unselected patients with suspected lung cancer, achieving even lower sensitivity and specificity. They recruited 93 consecutive patients with suspected lung cancer, all benign or malignant lung disease; none were healthy at the time of inclusion. ...
... However, the studies differed significantly with respect to sample types and storage methods. In the study by Cornu et al. (2011), the liquid urine samples were stored for an unspecified time period at À4 C versus the À20 C used by Gordon et al. (2008), Amundsen et al. (2014), andElliker et al. (2014), respectively, for 5 months, 2-4 weeks, and 1 day to 6 months, and the À40 C for 5 months reported in the study of Willis et al. (2004). We cannot exclude the possibility that temperature-and time-dependent variations have occurred in VOC concentrations (Mochalski et al., 2015). ...
... Different techniques for storage of breath samples were also found among the studies. Breath samples were stored at room temperature for 2-4 weeks in the studies by Amundsen et al. (2014) and Ehmann et al. (2012) (in this last case for an unspecified time period). In the Willis et al. (2004) study, breath samples were instead stored under refrigeration at 4 C until for an unspecified period of time before they were analyzed, whereas Gordon and colleagues (2008) stored this type of samples at À20 C for 5 months, and then at À18 C for an unspecified duration of time. ...
Article
Early diagnosis of cancer using effective screening methods is crucial for successful treatment. Recently, much attention has been given to the use of odors emitted in the form of volatile organic compounds (VOCs) as diagnostic biomarkers. Studies on special training of dogs to detect different cancers using various odor samples (breath, urine, cancer tissue) have provided promising results. This systematic review highlights the scientific reports testing canine olfaction to detect cancer, dividing them according to the cancer’s primary site. Several lines of evidence suggest that dogs may play a critical role in cancer research and diagnosis, eventually be major contributors to a reduction in mortality for certain cancers. Future directions that this field of research should take include efforts to overcome some methodological weaknesses and a certain heterogeneity of performance found across the different studies. Finding adequate responses to the challenges that lie ahead requires also a clear disclosure of what chemical compounds dogs respond to and the quantity of these compounds. Finally, the welfare of dogs involved in these practices should be considered.
... There are few published data on canine scent detection of cancer in general, or lung cancer in particular. Among the cancer types investigated were breast cancer [18,19], prostate cancer [19][20][21], colorectal cancer [22], melanomas [23] and lung cancer [18,24,25]. The results have been promising, though, especially from Ehmann et al [24] and McCulloch et al [18], who reported that trained dogs detected lung cancer with high sensitivity and specificity. ...
... The results have been promising, though, especially from Ehmann et al [24] and McCulloch et al [18], who reported that trained dogs detected lung cancer with high sensitivity and specificity. On the other side, Amundsen et al reported markedly lower specificities in unselected patients at risk [25]. ...
... The patients' cancer stage, age, smoking habits and most recently eaten meals did not influence the dogs' diagnostic performance. Breath seems to serve as a better sample for canine discrimination than urine, which was also proposed as a potentially good source of endogenously produced VOCs [19,25]. The advantages and disadvantages learned from existing studies on the canine method were recently summarized by Jezierski et al [26]. ...
Article
The prognosis in lung cancer depends largely on early stage detection, and thus new screening methods are attracting increasing attention. Canine scent detection has shown promising results in lung cancer detection, but there has only been one previous study that reproduces a screening-like situation. Here breath samples were collected from 122 patients at risk for lung cancer (smokers and ex-smokers); 29 of the subjects had confirmed diagnosis of lung cancer but had not yet been treated and 93 subjects had no signs or symptoms of lung cancer at the time of inclusion. The breath samples were presented to a trained sniffer dog squadron in a double-blind manner. A rigid scientific protocol was used with respect to earlier canine scent detection studies, with one difference: instead of offering one in five positive samples to the dogs, we offered a random number of positive samples (zero to five). The final positive and negative predictive values of 30.9% and 84.0%, respectively, were rather low compared to other studies. The results differed from those of previous studies, indicating that canine scent detection might not be as powerful as is looked for in real screening situations. One main reason for the rather poor performance in our setting might be the higher stress from the lack of positive responses for dogs and handlers.
... Moreover, their olfactory ability enables them to differentiate biological samples including urine, blood, faeces, and tissue from cancer patients and from healthy people by their sniffing ability [5][6][7][8][9][10][11][12][13]. A further example is the detection of lung cancer using breath samples [14][15][16][17][18][19]. In principle, the use of breath has the advantage of being a non-invasive sampling procedure. ...
... It is possible that the dogs learned to identify the individual odour samples from A549 and Lu7466 during training instead of detecting a common odour of two different lung cancer cell lines kept in vitro. A number of authors reported on sniffer dogs' ability to discriminate between samples of urine, blood and breath from cancer patients and from healthy controls, in particular in the case of lung cancer [14][15][16][17][18][19]. In contrast, we observed that dogs were not able to distinguish between the odours of two different lung cancer cell lines kept in vitro from their culture medium. ...
Article
Full-text available
In vitro cultured lung cancer cell lines were investigated regarding the possible identification of volatile organic compounds as potential biomarkers. Gas samples from the headspace of pure culture medium and from the cultures of human lung adenocarcinoma cell lines A549 and Lu7466 were exposed to polypropylene fleece in order to absorb odour components. Sniffer dogs were trained with loaded fleeces of both cell lines, and honey bees were trained with fleeces exposed to A549. Afterwards, their ability to distinguish between cell-free culture medium odour and lung cancer cell odour was tested. Neither bees nor dogs were able to discriminate between odours from the cancer cell cultures and the pure culture medium. Solid phase micro extraction followed by gas chromatography with mass selective detection produced profiles of volatiles from the headspace offered to the animals. The profiles from the cell lines were largely similar; distinct differences were based on the decrease of volatile culture medium components due to the cells' metabolic activity. In summary, cultured lung cancer cell lines do not produce any biomarkers recognizable by animals or gas chromatographic analysis.
... Studies have shown that when dogs were trained using the AFC task of one S+ and four S-samples, and then tested with randomized numbers of S+ and S-samples, the sensitivity and specificity of their performance deteriorated significantly (Amundsen et al. 2014;Hackner et al. 2016). This illustrates the importance of training and testing the dogs with randomized samples The AFC method also has a disadvantage due to a memory load it may impose on the detection dog. ...
... It is likely that the scent profile changes between samples from patients with an advanced vs. an earlier stage of disease. Amundsen et al. (Amundsen et al. 2014) showed that the dogs' performance is affected when they are tested with patients suspected to have different stages and forms of lung cancer. This finding highlights the importance of training the dogs not only with samples from patients with an advanced or malignant disease but with samples from benign stages of disorders. ...
Article
Full-text available
Biomedical scent detection dogs identify the scent profiles of diseases, such as cancer, diabetes or pathogenic micro-organisms. What the field of biomedical scent detection has been lacking, however, is the assessment of the method from the point of view of a health technology. All health technologies undergo a thorough evaluation of safety, clinical effectiveness and costs, as well as ethical, social, organizational and legal evaluations in some cases. Passing these regulatory controls is a pre-requisite before a technology is approved for use in decision-making about patient outcomes. Biomedical scent detection has a lot of attractive qualities, such as the sensitivity and specificity of the dogs’ noses, safety and relative cost-effectiveness. But the method also has various challenges, in particular regarding its clinical effectiveness. The most pertinent issues to address before the dogs would pass as a health technology are standardization the training techniques, both intra- and inter-dog reproducibility, and generalization of the detection task to early stages of disease progression. We suggest setting realistic goals in terms of what the dogs can and cannot do and a collaborative approach between clinicians and animal psychophysicists.
... The use of biomedical detection dogs for various infectious and non-infectious diseases like Helicobacter pylori [7], different cancer types [8][9][10][11][12][13][14][15][16][17], hypoglycaemia in diabetes mellitus patients [18][19][20], epileptic seizures [21], bacteriuria [22], bovine virus diarrhoea [23], COVID-19 [24][25][26][27][28][29][30][31][32][33], Malaria [34] and Clostridium difficile-infections [35] is still in its infancy ( Table 1). Most of these studies indicate a disease-specific body odour or a specific volatile organic compound (VOC)-pattern associated with metabolic changes secondary to an infection [36]. ...
... Studies with trained sniffer dogs achieved very different results in the identification of different cancer types, such as bladder, prostate or ovarian cancer, lung and breast cancer as well as colorectal neoplasms. Diagnostic accuracies varied with sensitivities ranging from 19 to 99% and specificities from 73 to 99% when compared to histopathology [8][9][10][11][12][13][14][15][16][17]. Different sample materials were used for presentation, e.g. ...
Article
Full-text available
The extraordinary olfactory sense of canines combined with the possibility to learn by operant conditioning enables dogs for their use in medical detection in a wide range of applications. Research on the ability of medical detection dogs for the identification of individuals with infectious or non-infectious diseases has been promising, but compared to the well-established and–accepted use of sniffer dogs by the police, army and customs for substances such as money, explosives or drugs, the deployment of medical detection dogs is still in its infancy. There are several factors to be considered for standardisation prior to deployment of canine scent detection dogs. Individual odours in disease consist of different volatile organic molecules that differ in magnitude, volatility and concentration. Olfaction can be influenced by various parameters like genetics, environmental conditions, age, hydration, nutrition, microbiome, conditioning, training, management factors, diseases and pharmaceuticals. This review discusses current knowledge on the function and importance of canines’ olfaction and evaluates its limitations and the potential role of the dog as a biomedical detector for infectious and non-infectious diseases.
... However, according to the recommendation, this reinforcement shall be diminished to be intermittent, for the feature practical use. For the training and testing setup, the samples were placed in a lineup in most of the previous studies, but a few were arranged in the circle [37]. Testing of four to seven samples can be recommended, since more samples may result in a lower probability of correct indication [30]. ...
... Testing of four to seven samples can be recommended, since more samples may result in a lower probability of correct indication [30]. The positive samples were used mostly one, but one study applied various target samples from one to six [37]. In our current experiment, one positive out of four control samples was arranged in the lineup, and this method is in line with the previous reports. ...
Article
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Background: Breast cancer is a leading cause of cancer death worldwide. Several studies have demonstrated that dogs can sniff and detect cancer in the breath or urine sample of a patient. This study aims to assess whether the urine sample can be used for breast cancer screening by its fingerprints of volatile organic compounds using a single trained sniffer dog. This is a preliminary study for developing the "electronic nose" for cancer screening. Methods: A nine-year-old female Labrador Retriever was trained to identify cancer from urine samples of breast cancer patients. Urine samples from patients histologically diagnosed with primary breast cancer, those with non-breast malignant diseases, and healthy volunteers were obtained, and a double-blind test was performed. Total of 40 patients with breast cancer, 142 patients with non-breast malignant diseases, and 18 healthy volunteers were enrolled, and their urine samples were collected. Results: In 40 times out of 40 runs of a double-blind test, the trained dog could correctly identify urine samples of breast cancer patients. Sensitivity and specificity of this breast cancer detection method using dog sniffing were both 100%. Conclusions: The trained dog in this study could accurately detect breast cancer from urine samples of breast cancer patients. These results indicate the feasibility of a method to detect breast cancer from urine samples using dog sniffing in the diagnosis of breast cancer. Although the methodological standardization is still an issue to be discussed, the current result warrants further study for developing a new breast cancer screening method based on volatile organic compounds in urine samples.
... There is science-based evidence that dogs are able to identify cancer specific odors in breath, blood, and urine samples of cancer patients (2)(3)(4). Although some studies reported promising sensitivities (71-99%) and specificities (78-98%) (5)(6)(7)(8), other studies described discouraging test characteristics (sensitivities: 3-71% and specificities: 8-53%) and discussed this approach more critically (4,(9)(10)(11)(12). These controversial results led to the question whether there are specific volatile organic compounds (VOCs) that are characteristic for a certain type of cancer cell or for metabolic processes in patients suffering from cancer. ...
... The results of the studies differ substantially. Whilst McCulloch et al. (5) found a sensitivity and specificity of 99% in detection of positive breath samples on lung cancer patients, the study by Amundsen et al. (11) revealed a mere 55.6% sensitivity and 8.3% specificity for small cell lung cancer. For a review of studies on lung cancer detection by detection dogs refer to Pirrone and Albertini (3). ...
Article
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Early and reliable diagnostic test is essential for effective therapy of lung cancer. Volatile organic compounds that are characteristic for cancer could serve as valuable biomarkers in cancer diagnosis. Both trace analytical and detection dog approaches give some evidence for the existence of such biomarkers. In this proof of concept, study dogs and trace analysis were implemented in combination to gain more information concerning cancer biomarkers. Two dogs were trained to distinguish between absorbed breath samples of lung cancer patients and healthy persons and succeeded with correct identification of patients with 9/9 and 8/9 and correct negative indications from of 8/10 and 4/10 samples from healthy individuals. A recent observational study found that breath samples from lung cancer patients showed an increase in 1-butanol, 2-butanone, 2-pentanone, and hexanal. Synthetic air samples were therefore fortified with these compounds and adsorbed to a fleece. Tested against breath samples from healthy probands, on presentation to the dogs these synthetic samples provoked an indication in three out of four samples. We were able to demonstrate that a combination of the natural nose of a dog and a trace analytic technique can be a valuable concept in the search for cancer biomarkers.
... Numerous studies have demonstrated the ability of canines to detect cancer in humans using their olfactory sense. 1,6 These experiments were conducted with the goal of identifying the compounds that specially trained dogs detect in the breath condensates of patients with breast or lung cancer. The LECOM Bradenton research lab team was previously able to characterize biomarkers isolated from breath condensates of patients with confirmed tumors as both small (<3 kDa) and hydrophobic, and large (>3kDa) and possibly proteinaceous. 2 Only relatively hydrophobic molecules were detected as potential cancer biomarkers. ...
... al., reported evidence of involvement of pathogenic exosomal biomolecules, containing microRNA and proteins, in human malignancies. 6 Our preliminary findings may indicate potential exosomal involvement, but repeated tests with more samples and controls will be necessary to confirm the reproducibility and the validity of results. Future experiments may then be used to further isolate the biomolecules via ultracentrifugation, microfiltration, SDS-PAGE, mass spectrometry, and/or Western blot assays. ...
... To date, however, a specific study has been not performed yet for discrimination of mesothelioma and asbestosis and in general of lung cancer. Only one patient with mesothelioma was included by Amundsen T et al. 2014 in the cohort of 93 patients for which canine olfactory test was performed on urine and breath samples in a double-blinded manner [102]. The test resulted in 99% sensitivity in the discrimination between cancer patients and healthy individuals but not specific comment was reported from authors on the case of mesothelioma. ...
... To date, however, a specific study has been not performed yet for discrimination of mesothelioma and asbestosis and in general of lung cancer. Only one patient with mesothelioma was included by Amundsen T et al. 2014 in the cohort of 93 patients for which canine olfactory test was performed on urine and breath samples in a double-blinded manner [102]. The test resulted in 99% sensitivity in the discrimination between cancer patients and healthy individuals but not specific comment was reported from authors on the case of mesothelioma. ...
Article
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Malignant pleural mesothelioma (MPM) is a rare neoplasm related to asbestos exposure and with high mortality rate. The management of patients with MPM is complex and controversial, particularly with regard to early diagnosis. In the last few years, breath analysis has been greatly implemented with this aim. In this review the strengths of breath analysis and preliminary results in searching breath biomarkers of MPM are highlighted and discussed, respectively. Through a systematic electronic literature search, collecting papers published from 2000 until December 2018, fifteen relevant scientific papers were selected. All papers considered were prospective, comparative, observational case–control studies although every single one pilot and based on a relatively small number of samples. The identification of diagnostic VOCs pattern, through breath sample characterization and the statistical data treatment, allows to obtain a strategic information for clinical diagnostics. To date the collected data provide just preliminary information and, despite the promising results and diagnostic accuracy, conclusions cannot be generalized due to the limited number of individuals included in each cohort study. Furthermore none of studies was externally validated, although validation process is a necessary step towards clinical implementation. Breathomics-based biomarker approach should be further explored to confirm and validate preliminary findings and to evaluate its potential role in monitoring the therapeutic response.
... However, larger prospective and blinded studies are needed and a number of technical issues have yet to be addressed.Case reports and a few small studies on dogs able to smell cancer in humans53,[73][74][75] have raised interest in training sniffer dogs to detect lung cancer using breath samples from patients. However, only a few prospective trials with divergent results have been published so far.17,61,76,77 McCulloch et al.17 used 55 lung cancer and 83 healthy control breath samples for training and blinded testing, reporting a sensitivity and specificity of 99% each, independent of the disease stage. ...
... COPD, smoking and food intake did not influence the dogs' accuracy. Interestingly, accuracy was best in TNM stage I (100%) and worst in stage IV (63%), suggesting possible changes in VOC by inflammation or necrosis in advanced tumours.Compared with these promising results, Amundsen et al.77 report rather discouraging data on the ability of dogs to detect lung cancer in an unselected cohort of 93 patients. Sixty-three patients were diagnosed with lung malignancies; the other 30 patients had benign diseases, with the exception of one patient with a history of urinary bladder cancer. ...
Article
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This review considers exhaled breath analysis, a non-invasive, widely applicable and cost-effective technique that holds great potential for evolving into a future screening tool for lung cancer and other diseases. Exhaled human breath contains thousands of volatile and non-volatile chemical compounds, which are products of metabolic processes and subject to changes in composition and concentration as a result of carcinogenesis. In the last decade, the analysis of volatile organic compounds (VOCs) has gained increasing interest because of the development of new technologies that might allow for detection of certain VOC biomarkers or patterns indicative of lung cancer. We provide an overview of the chemical analytical and sensor array technologies currently available for VOC analysis, including statistical methods implemented for the analysis of complex VOC patterns, and discuss issues of exhaled breath sampling and storage. Furthermore, we summarize the literature on exhaled breath analysis in lung cancer and discuss the results, limitations and future perspectives. We also briefly review the literature on sniffer dogs trained to detect lung cancer from human breath samples. In conclusion, even though certain issues have yet to be addressed and large randomized blinded studies are still lacking, there is evidence that exhaled breath analysis may be a promising tool for lung cancer screening.
... Aside from a scent platform with moving parts that can present cancer samples to dogs (Fischer-Tenhagen, Wetterholm, Tenhagen, & Heuwieser, 2011), applied work using adapted operant chambers is generally purely manual. Carousel or line systems, for example, have been used with canines to detect standard chemicals (Concha et al., 2014) or the presence of cancer (Amundsen et al., 2014). A recently developed apparatus (Mancini, Harris, Aengenheister, & Guest, 2015) measures the duration and amount of pressure dogs put on a nose plate when sniffing cancer samples. ...
Article
In this study, we trialed the use of a semiautomated line cage with African pouched rats for scent-detection tasks. The apparatus was a 2100 × 410 × 520-mm cage with 10 wells in the floor, under which samples were loaded. A nose-poke response was recorded by an infrared beam. Breaking this beam for a predetermined duration over a target sample triggered automatic delivery of a food pellet. We used a library of scents commonly used in the fragrance industry as stimuli. Ten rats were trained to discriminate a target from 9 other scents, and demonstrated a mean sensitivity of 94.23% and specificity of 95.1% at the conclusion of training. The value of measuring subthreshold responses and the importance of conducting research with controlled samples is discussed, as is the potential application of this technology to other scent-detection problems.
... Кинологическая одорологическая диагностика (КоД) рекомендована для скрининга онкозаболеваний [5]. Сообщений о применении кинологического метода диагностики в клинической онкологии в отечественной научной литературе мы не встретили. ...
Article
Full-text available
There is presented a possibility of canine otorhologic diagnosis of breast cancer based on presentation of odour material to service dogs: venous blood, urine and sweatfat secretions of female patients. The examination of odour material of ill women and control groups the sensitivity of the test was at the level of 0,94-0,98, specificity of 0,92 and 1,0 the predictive value of a positive result of 0,96-1,0 and negative 0,94-1,0, which significantly exceeded the diagnostic capabilities of mammography. On the basis of otorhologic study of sweatfat secretions there was showed high specificity of identifying patients with breast cancer among some other types of pathology including nodal mastopathy. A possibility of using olfactory capabilities of dogs when organizing mass screening tests is discussed.
... Both canines and e-noses can detect volatile organic compounds (VOCs) in biological specimens. It is well recognized that dogs can perceive spe- ciic VOCs in several samples, such as urine, expired breath, blood and stool [162][163][164][165][166]. For instance, diverse VOCs have been identiied in the breath of individuals afected by lung, ovar- ian, prostate, bladder and colorectal tumor [167][168][169][170]. ...
... Both canines and e-noses can detect volatile organic compounds (VOCs) in biological specimens. It is well recognized that dogs can perceive spe- ciic VOCs in several samples, such as urine, expired breath, blood and stool [162][163][164][165][166]. For instance, diverse VOCs have been identiied in the breath of individuals afected by lung, ovar- ian, prostate, bladder and colorectal tumor [167][168][169][170]. ...
... When it finally got excised, it turned out to be a malignant melanoma [12]. Since then, at least five studies with high quality and adequate design have been published (double-blind, randomized, controlled) to proof the efficacy of canine scent detection of cancer, sometimes referred as 'pet scan' [13][14][15][16][17]. The results are largely varying, although it is difficult to compare the figures directly, since the studies differ methodically in many aspects. ...
Article
Recent literature has touted the use of canine olfaction as a diagnostic tool for identifying pre-clinical disease status, especially cancer and infection from biological media samples. Studies have shown a wide range of outcomes, ranging from almost perfect discrimination, all the way to essentially random results. This disparity is not likely to be a detection issue; dogs have been shown to have extremely sensitive noses as proven by their use for tracking, bomb detection and search and rescue. However, in contrast to analytical instruments, dogs are subject to boredom, fatigue, hunger and external distractions. These challenges are of particular importance in a clinical environment where task repetition is prized, but not as entertaining for a dog as chasing odours outdoors. The question addressed here is how to exploit the intrinsic sensitivity and simplicity of having a dog simply sniff out disease, in the face of variability in behavior and response.
... In two studies, the number of samples in each run differed between training and testing (Cornu et al., 2011;Horvath et al., 2013). Two reports provided insufficient information regarding the similarity of training and testing conditions (Amundsen et al., 2014;Dehlinger et al., 2013). ...
Article
Animal olfactory detection of human diseases has attracted an increasing amount of interest from researchers in recent years. Because of the inconsistent findings reported in this body of research and the complexity of scent detection research, it is difficult to ascertain the potential value of animal detectors in operational diagnostic algorithms. We have outlined key factors associated with successful training and evaluation of animals for operational disease detection and, using these key factors as points for comparison, conducted a systematic review of the research in this area. Studies that were published in peer-reviewed outlets and that described original research evaluating animals for detection of human diseases were included in the review. The majority of relevant studies have assessed dogs as detectors of various forms of cancer. Other researchers have targeted bacteriuria, Clostridium difficile, hypoglycemia, and tuberculosis. Nematodes and pouched rats were the only exceptions to canine detectors. Of the 28 studies meeting inclusion criteria, only 9 employed operationally feasible procedures. The most common threat to operational viability was the use of a fixed number of positive samples in each sample run. Most reports included insufficient information for replication or adequate evaluation of the validity of the findings. Therefore, we have made recommendations regarding the type of information that should be included when describing research in this area. The results of this systematic review suggest that animal detectors hold promise for certain diagnostic applications but that additional research evaluating operationally viable systems for olfactory detection of human diseases is necessary.
... Zo hadden 5 getrainde honden een sensitiviteit en specificiteit van maar liefst 99% voor het herkennen van uitgeademde lucht van longkankerpatiënten, onafhankelijk van ziektestadium (tabel 1). 2 In 2 latere, grotere onderzoeken werden deze indrukwekkende resultaten niet gehaald; hier varieerde de sensitiviteit van 56-71% en specificiteit van 8-93%. 3,4 Vergelijkbare studies zijn inmiddels voor vele vormen van kanker gedaan, met opnieuw sterk wisselende resultaten. Voor detectie van colorectaalkanker in feces of uitgeademde lucht, ovariumcarcinoom in weefsel of bloedplasma, en prostaatkanker in urine worden sensitiviteiten en specificiteiten van ruim boven de 90% beschreven, opvallend genoeg vaak ongeacht het ziektestadium en soms zelfs wanneer de tumor al radicaal verwijderd is. ...
Article
- Infectious diseases and cancer change a patient's metabolism and hence the metabolic compounds produced. The composition of volatile organic compounds (VOCs) in exhaled breath or urine or stool samples can therefore be characteristic of a particular disease. - In recent years many studies have been conducted into the training of animals, including dogs, to recognise diseases by smell. Besides trained animals, electronic noses (e-noses) are also being developed. These devices can identify disease-specific odour profiles in VOCs.- Although the results of research in the field of scent diagnosis are promising, the medical community remains largely sceptical. We discuss applications of scent detection as a diagnostic tool in modern medicine.- Conflict of interest and financial support: none declared.
... There is some evidence that dogs are able to identify cancer-specific odors in breath, blood, and urine samples of cancer patients. Some studies reported high sensitivities (71-99%) and specificities (78-98%) (McCulloch et al. 2006;Buszewski et al. 2012;Ehmann et al. 2012;Horvath et al. 2013) while others described discouraging test characteristics (sensitivities: 3-71% and specificities: 8-53%) and discussed the ability of dogs to identify cancer more critically (Willis et al. 2004;Gordon et al. 2008;Amundsen et al. 2014;Elliker et al. 2014). These controversial results of studies on cancer diagnostic with dogs led us to the question if and how dogs can identify a common odor (e.g. a lung cancer biomarker) in a group of samples (e.g. ...
Article
In this study, a standardized experimental set-up with various combinations of herbs as odor sources was designed. Two training approaches for sniffer dogs were compared; first, training with a pure reference odor, and second, training with a variety of odor mixtures with the target odor as a common denominator. The ability of the dogs to identify the target odor in a new context was tested. Six different herbs (basil, St. John's wort, dandelion, marjoram, parsley, ribwort) were chosen to produce reference materials in various mixtures with (positive) and without (negative) chamomile as the target odor source. The dogs were trained to show 1 of 2 different behaviors, 1 for the positive, and 1 for the negative sample as a yes/no task. Tests were double blind with one sample presented at a time. In both training approaches, dogs were able to detect chamomile as the target odor in any presented mixture with an average sensitivity of 72% and a specificity of 84%. Dogs trained with odor mixture containing the target odor had more correct indications in the transfer task.
... the results of previous studies that have indicated that dogs can be rapidly trained to detect the pathophysiologic metabolic changes of cancers through olfaction. [13][14][15][16][17][18][19] Current early detection screening modalities have the potential to decrease morbidity and mortality from lung cancer; however, their sensitivity and specificity are low. New, less-invasive, cost-effective methods with greater sensitivity and specificity are needed. ...
Article
Full-text available
Context: Early detection provides the best opportunity for lung cancer survival; however, lung cancer is difficult to detect early because symptoms do not often appear until later stages. Current screening methods such as x-ray and computed tomographic imaging lack the sensitivity and specificity needed for effective early diagnosis. Dogs have highly developed olfactory systems and may be able to detect cancer in its primary stages. Their scent detection could be used to identify biomarkers associated with various types of lung cancer. Objective: To determine the accuracy of trained beagles' ability to use their olfactory system to differentiate the odor of the blood serum of patients with lung cancer from the blood serum of healthy controls. Methods: Over the course of 8 weeks, operant conditioning via clicker training was used to train dogs to use their olfactory system to distinguish blood serum from patients with malignant lung cancer from blood serum from healthy controls in a double-blind study. After training, non-small cell lung cancer and healthy control blood serum samples were presented to the dogs, and the sensitivity and specificity of each dog were analyzed. Results: Four dogs were trained for the study, but 1 was unmotivated by training and removed from the study. Three dogs were able to correctly identify the cancer samples with a sensitivity of 96.7%, specificity of 97.5%, positive predictive value of 90.6%, and negative predictive value of 99.2%. Conclusion: Trained dogs were able to identify non-small cell lung cancer samples from healthy controls. The findings of this study provide a starting point for a larger-scale research project designed to explore the use of canine scent detection as a tool for cancer biomarkers.
... Over the past decade, the use of dogs to detect and alert to human health conditions has expanded. There is growing evidence that dogs can be trained to alert to human disease samples, including, but not limited to: bladder cancer (1), breast cancer (2), cervical cancer (3), colorectal cancer (4), lung cancer (2,(5)(6)(7), ovarian cancer (8,9), prostate cancer (10), melanoma (11), Clostridium difficile (12), and cystic fibrosis bacterial pathogens (13) [see Edwards et al. (14) for the most recent systematic review]. These studies employ a variety of human sample types, including breath, urine, blood plasma, excrement and sebum. ...
Article
Full-text available
Recent literature has demonstrated that dogs have the potential to detect, and communicate the presence of, various human diseases. However, there is a lack of investigation into whether commonplace training differences within the field could influence a dog's behavior during a biomedical detection task. Here we report on the behavior of four dogs trained to alert to blood plasma samples taken from individuals with ovarian cancer. One hundred trials per dog were selected from routine video recordings collected over a period of 13 months. Videos were coded frame by frame to quantify sample checking, alerting behavior, and durations of alert. Dogs had previously been trained to elicit a final response behavior once they had located the target odor. Two dogs had a “sit” response while the other two had a “stand-stare” response. Alert behavior was categorized as true positive (a correct alert to a cancer sample) or false positive (an incorrect alert to biological and non-biological controls and distractors). Hesitations were also recorded, where the dog either checks the sample twice or, spends a longer duration of time sniffing the sample than a true pass without carrying out their final response. Results show individual variation in the total frequency of false alerts elicited. However, the rate of hesitations appears to be influenced by alert style, with stand-stare dogs carrying out 40 and 32, respectively (total = 72) and sit dogs carrying out 7 and 8, respectively (total = 15). The stand-stare dogs had a non-significant difference in the duration of their true and false positive alerts. In contrast, the sit dogs showed a significant difference (p < 0.001), maintaining their false alerts for, on average, two times the duration of their true alerts. Stand-stare dogs increased the duration of time spent in contact with the port when plasma samples were present, whereas sit dogs spent on average 0.3 s in contact with the port regardless of what sample type it contained. These findings suggest that the type of operant response a biomedical detection dog has been trained may influence their sample checking and response behavior.
... L'analyse de l'air expiré par des chiens a été effectué dans différents cas : cancer du poumon [138][139][140][141], cancer du sein [140,141], cancer colorectal [142], mélanome [141]. C'est également le cas pour les nez électroniques utilisés pour étudier les COV dans l'air expiré pour l'asthme [143][144][145][146], le cancer du poumon [147][148][149][150], et de nombreuses autres pathologies [124]. ...
Thesis
L’air expiré présente un intérêt pour des applications médicales comme le dépistage, le suivi de pathologies ou d’expositions. En effet, cet échantillon contient des marqueurs volatils endogènes ou exogènes et son prélèvement est non invasif. Même si le prélèvement est simple, la complexité et la variabilité de l’air expiré expliquent le peu de tests autorisés par les autorités sanitaires.Cette thèse s’est intéressée à deux outils analytiques pour l’analyse de l’air expiré : une puce de préconcentration et la chromatographie en phase gazeuse intégralement bidimensionnelle. Ces deux techniques, peu explorées jusqu’à présents dans ce domaine, peuvent présenter un intérêt en simplifiant le prélèvement et en permettant une analyse plus exhaustive des marqueursLe travail effectué sur la puce de préconcentration a montré que les micropréconcentrateurs fabriqués au laboratoire prélèvent et injectent des mélanges de gaz modèles et des échantillons d’air expiré avec des variabilités proches des systèmes de laboratoires. De plus, nos travaux ont montré que ces micropréconcentrateurs présentent deux avantages majeurs en réduisant les volumes d’échantillon nécessaires et en s’intégrant dans des systèmes simples, portables et fonctionnant sur batterie. Afin d’illustrer leur intérêt sur un cas réel simple, nous avons utilisé ces micropréconcentrateurs pour étudier trois marqueurs du tabagisme dans l’air expiré de trois fumeurs et de trois non-fumeurs et suivre les cinétiques de ces composés dans l’air expiré d’une personne. Finalement, nous avons effectué un travail préliminaire d’intégration dans des échantillonneurs dédiés afin d’exploiter les avantages des micropréconcentrateurs pour le prélèvement de l’air expiré et tenter d’obtenir un prélèvement sur une expiration unique.Nous avons ensuite choisi et reproduit une architecture de modulateur fluidique simple, pertinente pour la miniaturisation, basée sur un Dean’s switch. Nous avons montré que ce modulateur décrit en 2016 était compatible avec une injection par thermodésorption et comparé ses performances à la GC simple pour l’analyse d’un même échantillon d’air expiré. Ceci a montré que cette architecture présente un intérêt en modulant des composés exhalés très volatils ce qui permet de nombreuses levées de coélution. Finalement, nous avons montré, grâce à des plans d’expériences, que l’amélioration des performances de ce modulateur nécessitait un contrôle minutieux des paramètres.Enfin, nous avons confronté nos outils à des échantillons d’une malade atteinte d’une maladie rare, la phénylcétonurie. Des échantillons d’espace de tête d’urine et d’air expiré de la patiente ont été prélevés. Les résultats, incomplets à ce stade, sont discutés dans le manuscrit.
... These results support the notion that watery stool samples could allow for higher detection rates due to their proximity to the physical location of the cancer in the body. Instead of using dogs to discriminate between healthy individuals and individuals known to have cancer, Amundsen et al. (2014) used canine olfaction to differentiate between malignant and benign tumors in individuals with suspected lung cancer (6). The dogs in this study were initially trained by learning the odor signature of lung cancer through exposure to malignant tumors and to urine of lung cancer patients. ...
Article
Olfactory cancer detection shows promise as an affordable, precise, and noninvasive way to screen for cancer. This review focuses on two methods of olfactory cancer detection: first, the ability of canines to differentiate between cancerous and healthy individuals through the use of biological samples and second, electronic nose technology that uses chemical sensors to detect known biomarkers in exhaled breath. This review summarizes and critiques past research and outlines future directions to improve understanding of both canine olfaction and electronic nose technology.
... In the last decade, the ability of canines to discriminate odors associated with cancer in humans has been increasingly reported (Pirrone and Albertini, 2017). Dogs have been trained to detect different types of cancers such as lung cancer (Amundsen et al., 2014), breast cancer (McCulloch et al., 2006), melanoma (Pickel et al., 2004), colorectal cancer (Sonoda et al., 2011), and bladder cancer (Willis et al., 2004). Other animal species are also able to distinguish disease odors in humans. ...
Article
This study sought to determine whether mice can differentiate, through urine odors, conspecifics with melanoma in early stages, when no clinical signs are detectable, from healthy animals. Forty male mice of the B57BL6 strain were urine donors before and after orthotopic inoculation with melanoma cells. Another group (35 males and 31 females), divided into two sub-groups were either tested for spontaneous preference for urine odor from donors with melanoma against urine odor of healthy conspecifics, or underwent operant conditioning training to discriminate between the two kinds of urine samples. Open-field and Y-maze tests were used initially to assess any spontaneous preference for urine of either type of donor, and subsequently a Y-maze test was used in discrimination training. During 5- minute tests, it was recorded which sample the mouse approached first, the latency to the first sniffing, the frequency of approaching, and the total duration of sniffing of each urine sample. No significant spontaneous preference for urine samples from animals with melanoma or from healthy animals were observed. However, in the open-field test, the male mice in the first trial more frequently approached the melanoma sample (P<0.05). Mice were successfully trained to discriminate between urine samples from donors with melanoma (with or without clinical symptoms) versus urine from healthy controls (P<0.001). GCMS analyses showed that, after the inoculation of melanoma cells, the concentration of n-hexane and methylene chloride decreased, ethyl acetate and methyl cyclopentane disappeared, and acetone and 1-methyl-6,7-dioksabicyclo [3.2.1]octane appeared, in urine samples analyzed. The study demonstrated that mice can discriminate the odor of melanoma in the urine of their conspecifics even before visible clinical melanoma symptoms appear. This finding is crucial as a rationale for further studies directed towards developing a noninvasive screening method for the early detection of a cancer, based on detection of volatile organic compounds.
... Likewise, the repeatedly reported detection of lung and other cancers in breath and urine of patients by sniffer dogs [32][33][34][35][36][37][38][39] remains completely unresolved with regards to the responsible volatile compounds. ...
Article
In recent years numerous reports have highlighted the options of chemical breath analysis with regard to non-invasive cancer detection. Certain volatile organic compounds (VOC) supposedly present in higher amounts or in characteristic patterns have been suggested as potential biomarkers. However, so far no clinical application based on a specific set of compounds appears to exist. Numerous reports on the capability of sniffer dogs and sensor arrays or electronic noses to distinguish breath of cancer patients and healthy controls supports the concept of genuine cancer-related volatile profiles. However, the actual compounds responsible for the scent are completely unknown and there is no correlation with the potential biomarkers suggested on basis of chemical trace analysis. It is outlined that specific features connected with the VOC analysis in breath - namely small concentrations of volatiles, interfering background concentrations, considerable sampling effort and sample instability, impracticability regarding routine application - stand in the way of substantial progress. The underlying chemical-analytical challenge can only be met considering the severe susceptibility of VOC determination to these adverse conditions. Therefore, the attention is drawn to the needs for appropriate quality assurance/quality control as the most important feature for the reliable quantification of volatiles present in trace concentration. Consequently, the advantages of urine as an alternative matrix for volatile biomarker search in the context of diagnosing lung and other cancers are outlined with specific focus on quality assurance and practicability in clinical chemistry. The headspace over urine samples as the VOC source allows adapting gas chromatographical procedures well-established in water analysis. Foremost, the selection of urine over breath as non-invasive matrix should provide considerably more resilience to adverse effects during sampling and analysis. The most important advantage of urine over breath is seen in the option to partition, dispense, mix, spike, store, and thus to dispatch taylor-made urine samples on demand for quality control measures. Although it is still open at this point if cancer diagnosis supported by non-invasively sampled VOC profiles will ultimately reach clinical application the advantages of urine over breath should significantly facilitate urgently required steps beyond the current proof-of-concept stage and towards standardisation.
... Studies of dog training show that given multiple possible cues by which dogs can solve a training task, dogs will learn to use the cue(s) most salient and accessible to them [e.g., (12)], and here it appears that the altered odor created by the dipstick was that cue. Urine was previously believed to be less susceptible to cross contamination and processing effects than more volatile media such as breath (13). It is widely acknowledged that ambient VOC's can contaminate breathe samples [e.g., (7)], but here we demonstrate that even for a liquid medium there is significant risk of cross contamination so standardized processing of samples is essential. ...
Article
Full-text available
Training new medical odors presents challenges in procuring sufficient target samples, and suitably matched controls. Organizations are often forced to choose between using fewer samples and risking dogs learning individuals or using differently sourced samples. Even when aiming to standardize all aspects of collection, processing, storage and presentation, this risks there being subtle differences which dogs use to discriminate, leading to artificially high performance, not replicable when novel samples are presented. We describe lessons learnt during early training of dogs to detect prostate cancer from urine. Initially, six dogs were trained to discriminate between hospital-sourced target and externally-sourced controls believed to be processed and stored the same way. Dogs performed well: mean sensitivity 93.5% (92.2–94.5) and specificity 87.9% (78.2–91.9). When training progressed to include hospital-sourced controls, dogs greatly decreased in specificity 67.3% (43.2–83.3). Alerted to a potential issue, we carried out a methodical, investigation. We presented new strategically chosen samples to the dogs and conducted a logistic regression analysis to ascertain which factor most affected specificity. We discovered the two sets of samples varied in a critical aspect, hospital-processed samples were tested by dipping the urinalysis stick into the sample, whilst for externally sourced samples a small amount of urine was poured onto the stick. Dogs had learnt to distinguish target aided by the odor of this stick. This highlights the importance of considering every aspect of sample processing even when using urine, often believed to be less susceptible to contamination than media like breath.
... From the papers extracted, two studies [20,21] reported on the training of sniffer dogs. Detection dogs are currently used to identify illegal substances, such as explosives or drugs, or to recognize missing persons in highly demanding environments. ...
Article
Full-text available
Lung cancer is the leading cause of cancer deaths worldwide. Its early detection has the potential to significantly impact the burden of the disease. The screening and diagnostic techniques in current use suffer from limited specificity. The need therefore arises for a reliable biomarker to identify the disease earlier, which can be integrated into a test. This test would also allow for the recurrence risk after surgery to be stratified. In this context, urine could represent a non-invasive alternative matrix, with the urinary metabolomic profile offering a potential source for the discovery of diagnostic biomarkers. This paper aims to examine the current state of research and the potential for translation into clinical practice.
... In several studies, sniffer dogs were trained to discriminate cancer samples (breath, urine, cancer tissue) in different media. Across published studies, a sensitivity of 78% and a specificity of 71.5% related to olfactory detection of lung cancer samples by sniffer dogs was reported [7][8][9][10][11]. Those study results are encouraging but published studies differ in terms of the experimental setup, kind of odor samples, sample collection methods, dogs' characteristics and dog training methods as well as in results presented in terms of detection sensitivity and specificity [12,13]. ...
Article
Full-text available
Background Lung cancer is the most common oncological cause of death in the Western world. Early diagnosis is critical for successful treatment. However, no effective screening methods exist. A promising approach could be the use of volatile organic compounds as diagnostic biomarkers. To date there are several studies, in which dogs were trained to discriminate cancer samples from controls. In this study we evaluated the abilities of specifically trained dogs to distinguish samples derived from lung cancer patients of various tumor stages from matched healthy controls. Methods This single center, double-blind clinical trial was approved by the local ethics committee, project no FF20/2016. The dog was conditioned with urine and breath samples of 36 cancer patients and 150 controls; afterwards, further 246 patients were included: 41 lung cancer patients comprising all stages and 205 healthy controls. From each patient two breath and urine samples were collected and shock frozen. Only samples from new subjects were presented to the dog during study phase randomized, double-blinded. This resulted in a specific conditioned reaction pointing to the cancer sample. Results Using a combination of urine and breath samples, the dog correctly predicted 40 out of 41 cancer samples, corresponding to an overall detection rate of cancer samples of 97.6% (95% CI [87.1, 99.9%]). Using urine samples only the dog achieved a detection rate of 87.8% (95% CI [73.8, 95.9%]). With breath samples, the dog correctly identified cancer in 32 of 41 samples, resulting in a detection rate of 78% (95% CI [62.4, 89.4%]). Conclusions It is known from current literature that breath and urine samples carry VOCs pointing to cancer growth. We conclude that olfactory detection of lung cancer by specifically trained dogs is highly suggestive to be a simple and non-invasive tool to detect lung cancer. To translate this approach into practice further target compounds need to be identified.
... Dogs were also trained to recognize diseases in exhaled air, urine, feces, and cancer tissue samples from patients affected with different types of tumors: lung [160,[169][170][171][172][173], breast [169,174], prostate [175,176], ovary [177], bladder [178], and large intestine [179], and distinguish these samples from those taken from healthy patients. Dogs spontaneously detected melanoma developing in their owners and were able to identify not only melanoma developing on the patient's skin, but also detect cancer cells which were placed on the skin surface of healthy patients [180]. ...
Article
Full-text available
Olfaction in dogs is crucial for gathering important information about the environment, recognizing individuals, making decisions, and learning. It is far more specialized and sensitive than humans’ sense of smell. Using the strength of dogs’ sense of smell, humans work with dogs for the recognition of different odors, with a precision far exceeding the analytical capabilities of most modern instruments. Due to their extremely sensitive sense of smell, dogs could be used as modern, super-sensitive mobile area scanners, detecting specific chemical signals in real time in various environments outside the laboratory, and then tracking the odor of dynamic targets to their source, also in crowded places. Recent studies show that dogs can detect not only specific scents of drugs or explosives, but also changes in emotions as well as in human cell metabolism during various illnesses, including COVID-19 infection. Here, we provide an overview of canine olfaction, discussing aspects connected with anatomy, physiology, behavioral aspects of sniffing, and factors influencing the olfactory abilities of the domestic dog (Canis familiaris).
Chapter
Marketing specialists like to give new products exciting names and use comparisons that spark the imagination of the potential buyer. Many products have been compared to Star Trek technologies in name or description in the hopes that consumers will equate them with the space age items from the franchise. In most cases this is a stretch, but the XPrize Foundation currently is running a tricorder X Prize worth 10 million dollars. Teams must produce a small device to monitor vital signs and diagnose many diseases and conditions, all without the help of a medical professional. This is truly Star Trek-like. However it is incomplete. Star Trek tricorders are capable of collecting huge amounts of primary sensor data in many areas, including meteorology, biology, geology, geography, and materials sciences. To approximate these functions, smartphone applications and dongles are being developed that can sense all manner of environmental and physical data—even cancer, and then interpret the data for our use or collate it with other data on the Internet of Things.
Article
Full-text available
Experimental studies using trained dogs to identify breath odour markers of human cancer, published in the recent decade, have been analyzed and compared with the authors' own results. Particular published studies differ as regards the experimental setup, kind of odour samples (breath, urine, tumor tissue, serum), sample collection methods, dogs' characteristics and dog training methods as well as in results presented in terms of detection sensitivity and specificity. Generally it can be stated that trained dogs are able to distinguish breath odour samples typical for patients with lung cancer and other cancers from samples typical for healthy humans at a 'better than by chance' rate. Dogs' indications were positively correlated with content of 2-pentanone and ethyl acetate (r = 0.97 and r = 0.85 respectively) and negatively correlated with 1-propanol and propanal in breath samples (r = -0.98 and -0.87 respectively). The canine method has some advantages as a potential cancer-screening method, due to its non-invasiveness, simplicity of odour sampling and storage, ease of testing and interpretation of results and relatively low costs. Disadvantages and limitations of this method are related to the fact that it is still not known exactly to which chemical compounds and/or their combinations the dogs react. So far it could not be confirmed that dogs are able to sniff out early preclinical cancer stages with approximately the same accuracy as already diagnosed cases. The detection accuracy may vary due to failure in conditioning of dogs, decreasing motivation or confounding factors. The dogs' performance should be systematically checked in rigorous double-blind procedures. Recommendations for methodological standardization have been proposed.
Article
OBJECTIVE: To describe the use of, and attitudes toward, complementary therapy (CT) by parents of children with moderate to severe cerebral palsy. METHODS: Parents of 32 children with cerebral palsy (age 5-12 years) enrolled in a randomized trial of cranial osteopathy prospectively participated in semi-structured interviews in the home to explore the use of CT and views regarding access to and expectations of these therapies. Interview transcripts were analyzed thematically, and content analysis was used to determine the frequency of use of different therapies. RESULTS: Sixteen children (50%) had received one or more types of CT, although only three were currently receiving any CT. The primary reasons for trying CT were to reduce children's pain and improve physical function. Parents had limited knowledge of the range of, and possible indications for, CT and expressed concerns about CT safety and effectiveness. Practical considerations of time and cost were also identified. Some parents had strong beliefs about the benefits, and, overall, parents indicated a high level of commitment to finding any treatments, conventional or CT, to help their children. CONCLUSION: Parents of children with cerebral palsy want to help their child, but they need information, guidance, and practical support to facilitate their decision-making regarding the use of CT. A clearer understanding of factors predictive of optimal outcomes will enable resources to be targeted effectively.
Article
The aim of the article is to discuss question if the dogs and their olfactory systems can detect various kinds of human malignant tumours. These scientific experiments and hypotheses started more than 20 years ago. There are referring studies focused on the topic and overview of their results and success rate of dog's distinguishing ability, too. In special laboratory, dogs distinguish the scents from breath, tissues or other body fluids, from the cancer patients and healthy controls. The accuracy of detection was significant and does not depend on the phase of cancer or variety of malignity. All around the world the major part of studies are confirming that dogs are able to detect scent of tumour with high significant sensitivity and specificity. Concurrently these part is discussing field of study of electronic nose and using canine olfactory ability for distinguish another diseases.
Article
Scent-detection animals are routinely evaluated for detection accuracy for a wide range of targets. The obtained estimates of accuracy vary widely, even with the same species of detector (e.g., dogs) and target type (e.g., lung cancer). One factor that may contribute to these varied results is variability in the point at which the detection animals are transitioned to the accuracy test. If training is incomplete, a nonrepresentative estimate of the animal's potential performance will likely be obtained. Descriptions of evaluation research with scent-detection animals commonly include little information about the factors influencing the researchers’ decision to transition from training to testing. When this information is reported, the decision criteria are often problematic. Herein, we explore methods of evaluating when a detection animal is performing at or near the highest accuracy of which they are capable and, therefore, when it may be suitable to transition to an accuracy test. We then apply these methods to an applied scent-detection project in which dogs were being trained to classify breath samples according to the status of the sample donor as lung-cancer-negative or lung-cancer-positive. In this specific case, a quantitative model of acquisition was most informative. We recommend that researchers in this field apply and report on evaluations of acquisition when conducting and describing evaluation research with scent-detection animals.
Article
Nasal airflow plays a critical role in olfaction by transporting odorant from the environment to the olfactory epithelium, where chemical detection occurs. Most studies of olfaction neglect the unsteadiness of sniffing and assume that nasal airflow and odorant transport are "quasi-steady," wherein reality most mammals "sniff." Here, we perform computational fluid dynamics simulations of airflow and odorant deposition in an anatomically accurate model of the coyote (Canis latrans) nasal cavity during quiet breathing, a notional quasi-steady sniff, and unsteady sniffing to: quantify the influence of unsteady sniffing, assess the validity of the quasi-steady assumption, and investigate the functional advantages of sniffing compared to breathing. Our results reveal that flow unsteadiness during sniffing does not appreciably influence qualitative (gross airflow and odorant deposition patterns) or quantitative (time-averaged olfactory flow rate and odorant uptake) measures of olfactory function. A quasi-steady approximation is, therefore, justified for simulating time-averaged olfactory function in the canine nose. Simulations of sniffing versus quiet breathing demonstrate that sniffing delivers about 2.5 times more air to the olfactory recess and results in 2.5-3 times more uptake of highly- and moderately-soluble odorants in the sensory region per unit time, suggesting one reason why dogs actively sniff. Simulations also reveal significantly different deposition patterns in the olfactory region during inspiration for different odorants, and that during expiration there is little retronasal odorant deposition in the sensory region. These results significantly improve our understanding of canine olfaction, and have several practical implications regarding computer simulation of olfactory function.
Article
Purpose We sought to assess whether a dog can be trained to distinguish obstructive sleep apnea patients from healthy controls based on the olfactory detection of urine. Methods Urine samples were collected from 23 adult male obstructive sleep apnea patients and from 20 voluntary adult male volunteers. Three dogs were trained through reinforced operant conditioning. Results Two of the three dogs correctly detected two thirds of obstructive sleep apnea patients (p < 0.000194 and p < 0.000003, respectively). Conclusions We found that dogs can be trained to distinguish obstructive sleep apnea patients from healthy controls based on the smell of urine. Potentially, dogs could be utilized to identify novel biomarkers or possibly screen for obstructive sleep apnea.
Chapter
Native aquatic wildlife species are declining within their natural range worldwide. Simultaneously, invasive species now dominate many aquatic landscapes in most parts of the world. Both groups require effective and accurate monitoring to guide management actions. This chapter offers background information on the issues surrounding monitoring of threatened and invasive species in aquatic environments—with a focus on amphibians, otters, American mink, muskrats, nutria, waterfowl, and other aquatic birds. Present-day human and passive monitoring techniques are reviewed in regard to efficacy, accuracy, and resource intensity. Current and potential applications of detection dogs for these aquatic wildlife groups, as either stand-alone or supplementary monitoring techniques, are considered. Examples of known related uses of dogs are provided, and potential future applications for detection dogs are highlighted.
Article
Capitalizing on canine olfactory capacity is a promising strategy for detecting and diagnosing human, animal, and plant diseases. The purpose of this review was to assess the extent of current research in canine disease detection and to identify factors impacting detection success. In this systematic review and meta-analysis, multiple databases were searched for studies in which dogs were trained to detect diseases or health conditions for both plants and animals. Following PRISMA guidelines, 2109 non-duplicate studies were screened and 58 relevant studies identified. Most studies (n = 33, 57%) took place in Europe. Across all studies, 192 unique detection dogs were tested. The most numerous breed was Labrador Retrievers (n = 27, 14%). The median number of dogs per study was 2 (range: 1-20). To analyze experimental design and results, studies including multiple test paradigms were divided into sub-studies (n = 105). Lung cancer (n = 11, 22%) and prostate cancer (n = 14, 13%) were the most frequently studied conditions. Urine (n = 27, 26%) and breath (n = 15, 14%) were the most common sample materials. In 86% of sub-studies (n = 90), dogs were presented with sets of samples and 72% (n = 76) reported a constant number of samples per trial. The median number of samples per trial was 6 (range: 2-100). Of the sub-studies reporting a fixed number of positive samples (range: 1-10; n = 65), 91% (n = 59) presented one positive sample per trial. A plurality of sub-studies (n = 47, 45%) presented samples in a lineup. Sensitivity (median: 0.90; range: 0.17-1.0; n = 90) and specificity (median: 0.96; range: 0.08-1.0; n = 81) were the predominant measures of detection success. In some cases, study design may have influenced results. There was a positive relationship between specificity and the likelihood of a true negative response based on the number of samples per trial, and specificity was higher in studies that did not include a double blinded test than those that did. Dogs appear to have the capacity to detect disease via olfaction; yet the nascent nature of this discipline yields inconsistency in methodology and reporting.
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Distributed cognition generally refers to situations in which task requirements are shared among multiple agents or, potentially, off-loaded onto the environment. With few exceptions, socially distributed cognition has largely been discussed in terms of intraspecific interactions. This conception fails to capture some forms of group-level cognition among human and non-human animals that are not readily measured or explained in mentalistic or verbal terms. In response to these limitations, we argue for a more stringent set of empirically-verifiable criteria for assessing whether a system is an instance of distributed cognition: interaction-dominant dynamics, agency, and shared task orientation. We apply this framework to humans and working dogs, and contrast the human-dog socially distributed cognitive system with humans using non-biological tools and human interaction with draft animals. The human-dog system illustrates three operationalizable factors for classifying phenomena as socially distributed cognition and extends the framework to interspecies distributed cognition.
Article
Early detection of lung cancer (LC) is a priority since LC is characterized by symptoms mimicking other respiratory conditions, but remains the leading cause of oncological disease death. Properly trained dogs can perceive the volatile organic compounds (VOCs) related to cancer, thanks to their acute sense of smell. Dogs' use for LC detection could be advantageous: reliable trained dogs would represent a valuable, cost-effective, non-invasive method of screening, which gives a clear-cut yes/no response. However, whether sniffer dogs are able to maintain their discriminative capacity at long-term control, and in different types of environments, needs further investigation. In this study, we sought to test two hypotheses: firstly, if dogs can be trained to perceive LC-related VOCs in human urine, a substrate which may be a good candidate for large-numbers screening, and secondly, whether trained dogs retain their performance stable over time, even if the environment in which the tests are carried out varies. We have selected three family dogs that underwent a one-year training period (two weekly training sessions), by clicker training method. At the end of the training, dogs underwent two separate test phases, in two different locations, one year apart. All other procedures had been maintained unchanged. The donors of the samples submitted to the dogs were recruited by the European Institute of Oncology (IEO), Milan, Italy. Results show that dogs had different sensitivity (range: 45%-73%) and specificity rate (range: 89%-91%), and were deceived neither by lung conditions (that the dogs did not consider) nor by the existence of tumors in the beginning stage, that was correctly reported by dogs. The one-year interruption of the research work and the changes in the test environment did not induce statistically significant differences in the dogs' perceptive capacity. To our knowledge, so far, these issues have never been highlighted.
Article
Metal oxide based gas sensing is promising to realize the effective detection of formaldehyde from the breathing gas, which is of great significance to lung cancer monitoring in the budding period. Seeking for novel materials with controlled microstructure and surface characteristics, while improving the sensing limit is still a highly desirable challenge. In this work, the hierarchical porous LaFeO3 is explored for this purpose by using a low-cost, simple and mature method. By tuning the quantity of F108 structuring agent and calcined temperature, the corresponding gas-sensing properties can be adjusted and optimized. The results indicate that the LaFeO3 with 0.5 g F108 possess the best gas-sensing property with sensing response of 116 toward 50 ppm formaldehyde at 125 °C. Importantly, the trace detection capacity is as low as 50 ppb, which is among the lowest value in the record of formaldehyde detection. Further detailed analysis indicates that the special hierarchical porous structure with high surface area and pore volume should be responsible for the improved sensing performance. These results suggest that construct hierarchical porous structure is a promising method to attain superior gas-sensing properties and LaFeO3 can be potentially used for accurate, inexpensive, real-time, and painless detection of lung cancer.
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One of the most powerful tools in fighting cancer is early detection, as it has been strongly linked to greater chances of cancer survival. However, traditional cancer screening tests can cost hundreds if not thousands of dollars and are therefore not an affordable option for many marginalized populations. From a public health perspective, it is vital to research the use of inexpensive cancer detection so that low-resourced patients have greater access to affordable cancer screening. Numerous studies dating from the early 2000s to recent years have shown extensive evidence that the exceptional olfactory system of canines allows them to detect certain odors through exhaled breath condensate that are known to be biomarkers of a variety of cancers. In addition to providing a cheaper alternative to conventional cancer screening tests, the use of cancer sniffing dogs has other benefits, including great reliability and accuracy. There are a few major types of cancer for which the "cancer dog test" proved to be remarkably effective, particularly colorectal, ovarian, and lung cancers. The test is non-invasive unlike most previous detection methods, meaning that it is also a safer option for individuals seeking cancer screening. Although the use of cancer sniffing dogs does have certain limitations and scope for error, it would provide a more affordable and accessible option for cancer screening, making it especially beneficial to low-resourced populations.
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Background: Remote medical scent detection of cancer and infectious diseases with dogs and rats has been an increasing field of research these last 20 years. If validated, the possibility of implementing such a technique in the clinic raises many hopes. This systematic review was performed to determine the evidence and performance of such methods and assess their potential relevance in the clinic. Methods: Pubmed and Web of Science databases were independently searched based on PRISMA standards. We included studies aiming at detecting cancers and infectious diseases affecting humans with dogs or rats. We excluded studies using other animals, studies aiming to detect agricultural diseases, diseases affecting animals, and others such as diabetes and neurodegenerative diseases. Only original articles were included. Data about patients’ selection, samples, animal characteristics, animal training and testing configurations, and performances were recorded. Results: A total of 62 studies were included. Sensitivity and specificity varied a lot among studies: While some publications report low sensitivities of 17% and specificities around 29%, others achieve rates of 100% sensitivity and specificity. Only 6 studies were evaluated in a double-blind screening like situation. In general, the risk of performance bias was high in most evaluated studies, and the quality of the evidence found was low. Conclusions: Medical detection using animals’ sense of smell lacks evidence and performances so far to be applied in the clinic. What odours the animals detect is not well understood. Further research should be conducted, focusing on patient selection, samples (choice of materials, standardization), and testing conditions. Interpolations of such results to free running detection (direct contact with humans) should be taken with extreme caution.
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Dog has natural gift of better smelling power which can be exploited for several purposes and disease diagnosis is one amongst them. The work on the use of dog nose in disease diagnosis is in preliminary stage. The electronic noses/e-noses are sensor based physical devices which are used to detect and analyse the various volatile organic compounds (VOCs) specific for health disorders including cancer to metabolic and infectious diseases. The sensor based disease diagnosis is also in preliminary stage. The data generated through studies conducted on disease diagnosis using one of the best noses of the universe may improve the sensitivity and specificity of existing e-noses to add par and this refined artificial intelligence, web data bases and sophisticated hardware and software may play in future a major role in field of diagnosis, monitoring and surveillance of human and animal diseases.
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Should we let our smoking patients burn their cigarettes and our money? NLST¹ lacks information about counseling / smoking cessation treatment of eligible individuals before randomization: an ethical matter and against clinical practice guidelines. Many patients don´t quit due the lack of money, information, etc²; such patients may respond to brief motivational interventions. CXR in PA causes information loss, since nearly one-third of the lung fields is unacessible without the lateral view. This lessened CXR detection and therefore increased the difference between CXR and CT. This paper may cause pre-contemplation stage patients to rely on the screening, until the CT shows any suspect lesions, preventing them from quitting, making the screening less effective from the public health standpoint. Peto et al showed that cumulative risk by 75 years of age decreases if patients stop smoking around 60. Probably most smokers will consider themselves at elevated risk and may want to undergo yearly CT, increasing the costs for the health system. Smoking cessation is cost-effective and relevant both for clinical practice and public health, which might not hold entirely true for screening smokers with CT.
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The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009. The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds. A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% CI, 1.2 to 13.6; P=0.02). Screening with the use of low-dose CT reduces mortality from lung cancer. (Funded by the National Cancer Institute; National Lung Screening Trial ClinicalTrials.gov number, NCT00047385.).
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Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled breath of patients may represent the ideal specimen for future lung cancer screening. However, the clinical applicability of current diagnostic sensor technologies based on signal pattern analysis remains incalculable due to their inability to identify a clear target. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were applied. Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or chronic obstructive pulmonary disease (COPD)) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders. Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. Logistic regression identified two drugs as potential confounders. It must be assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer. Additional research efforts are required to overcome the current technical limitations of electronic sensor technologies to engineer a clinically applicable screening tool.
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According to the most recent global cancer statistics, the burden of malignancies continues to increase worldwide, so that there is a compelling need to reinforce the screening strategies and implement novel diagnostic approaches for early detection. Canines are widely used by police forces and civilian services for detecting explosives and drugs due to their superior olfactive apparatus, which is characterized by a detection threshold as low as parts per trillion. There is mounting evidence that dogs might be effectively trained to detect patients with various form of cancers due to the presence of a characteristic "odor signature". In particular, preliminary studies reported that appropriately trained dogs exhibit an extraordinary ability to detect melanoma as well as prostate, breast, ovary and lung cancers by recognizing a characteristic "odor signature" in body, urines, sweat, breath and even blood. The most problematic issue that has emerged so far is the large heterogeneity of performance across the different studies as well as within the same study, which might be dependent upon genetic characteristics or training methodology. This article is aimed to provide an overview of the available data on cancer sniffer dogs, highlighting the appealing perspectives and the potential drawbacks.
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Ovarian carcinoma represents about 4% of all cancers diagnosed in women worldwide. Mortality rate is high, over 50%, mainly due to late diagnosis. Currently there are no acceptable screening techniques available, although ovarian cancer belongs to the group of malignancies for which mortality could be dramatically reduced by early diagnosis.In a recently published study, we clearly demonstrated that human ovarian carcinoma tissues can be characterized by a specific odour, detectable by a trained dog. Another recent study confirmed these results using an electronic nose. In the present work, we examined whether the cancer-specific odour can also be found in the blood. Two specially trained dogs were used. Both ovarian cancer tissues and blood from patients with ovarian carcinoma were tested. The tissue tests showed sensitivity of 100% and specificity of 95%, while the blood tests showed sensitivity of 100% and specificity of 98%. The present study strongly suggests that the characteristic odour emitted by ovarian cancer samples is also present in blood (plasma) taken from patients with the disease. This finding opens possibilities for future screening of healthy populations for early diagnosis of ovarian carcinoma. A future challenge is to develop a sensitive electronic nose for screening of ovarian carcinoma by testing the blood/plasma to detect the disease at a stage early enough for treatment to be effective.
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Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers. Exhaled alveolar breath was collected from 177 volunteers aged 20-75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patient's data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS). The results showed that the nanosensor array could differentiate between 'healthy' and 'cancerous' breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types. The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.
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Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this study we compared the cytokine pattern of EBC of patients suffering from squamous cell lung carcinoma with that of healthy smokers. Breath condensates collected from 8 smoking lung cancer patients before receiving any anticancer treatment and 8 smokers without any clinical or radiological evidence of pulmonary tumors were used for antibody microarray analysis testing 120 cytokines simultaneously. Ninety-eight cytokines on the array gave a detectable signal in both groups. Cytokine levels were similar across the samples, and none of the cytokines exhibited a significant increase or decrease in cancer patients as compared to healthy subjects with similar smoking status, lung function, and airway inflammation. The results of this pilot study suggest that patients with squamous cell lung carcinoma cannot be distinguished from smokers with no pulmonary tumors based on EBC cytokine signals only.
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A potential strategy for diagnosing lung cancer, the leading cause of cancer-related death, is to identify metabolic signatures (biomarkers) of the disease. Although data supports the hypothesis that volatile compounds can be detected in the breath of lung cancer patients by the sense of smell or through bioanalytical techniques, analysis of breath samples is cumbersome and technically challenging, thus limiting its applicability. The hypothesis explored here is that variations in small molecular weight volatile organic compounds ("odorants") in urine could be used as biomarkers for lung cancer. To demonstrate the presence and chemical structures of volatile biomarkers, we studied mouse olfactory-guided behavior and metabolomics of volatile constituents of urine. Sensor mice could be trained to discriminate between odors of mice with and without experimental tumors demonstrating that volatile odorants are sufficient to identify tumor-bearing mice. Consistent with this result, chemical analyses of urinary volatiles demonstrated that the amounts of several compounds were dramatically different between tumor and control mice. Using principal component analysis and supervised machine-learning, we accurately discriminated between tumor and control groups, a result that was cross validated with novel test groups. Although there were shared differences between experimental and control animals in the two tumor models, we also found chemical differences between these models, demonstrating tumor-based specificity. The success of these studies provides a novel proof-of-principle demonstration of lung tumor diagnosis through urinary volatile odorants. This work should provide an impetus for similar searches for volatile diagnostic biomarkers in the urine of human lung cancer patients.
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Conventional diagnostic methods for lung cancer are unsuitable for widespread screening because they are expensive and occasionally miss tumours. Gas chromatography/mass spectrometry studies have shown that several volatile organic compounds, which normally appear at levels of 1-20 ppb in healthy human breath, are elevated to levels between 10 and 100 ppb in lung cancer patients. Here we show that an array of sensors based on gold nanoparticles can rapidly distinguish the breath of lung cancer patients from the breath of healthy individuals in an atmosphere of high humidity. In combination with solid-phase microextraction, gas chromatography/mass spectrometry was used to identify 42 volatile organic compounds that represent lung cancer biomarkers. Four of these were used to train and optimize the sensors, demonstrating good agreement between patient and simulated breath samples. Our results show that sensors based on gold nanoparticles could form the basis of an inexpensive and non-invasive diagnostic tool for lung cancer.
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In this article, we describe a device that we have developed, for both research and operational purposes, to assist handlers of sniffer dogs and improve efficiency of search. The device transmits sounds from the dog's muzzle area to a listener, enabling determination of whether the dog is actually sniffing during a search. Both the aural and the computerized sound analyses enable study of the dog's sniffing behavior under a variety of situations. Correlation of these data with the visually monitored behavior of the working dog contributes additional and important information and leads to a greater understanding of detector dogs' behavior and abilities.
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This paper describes the use of headspace solid-phase microextraction (SPME) combined with gas chromatography to identify the signature odors that law enforcement-certified detector dogs alert to when searching for drugs, explosives, and humans. Background information is provided on the many types of detector dog available and specific samples highlighted in this paper are the drugs cocaine and 3,4-methylenedioxy- N-methylamphetamine (MDMA or Ecstasy), the explosives TNT and C4, and human remains. Studies include the analysis and identification of the headspace "fingerprint" of a variety of samples, followed by completion of double-blind dog trials of the individual components in an attempt to isolate and understand the target compounds that dogs alert to. SPME-GC/MS has been demonstrated to have a unique capability for the extraction of volatiles from the headspace of forensic specimens including drugs and explosives and shows great potential to aid in the investigation and understanding of the complicated process of canine odor detection. Major variables evaluated for the headspace SPME included fiber chemistry and a variety of sampling times ranging from several hours to several seconds and the resultant effect on ratios of isolated volatile components. For the drug odor studies, the CW/DVB and PDMS SPME fibers proved to be the optimal fiber types. For explosives, the results demonstrated that the best fibers in field and laboratory applications were PDMS and CW/DVB, respectively. Gas chromatography with electron capture detector (GC/ECD) and mass spectrometry (GC/MS) was better for analysis of nitromethane and TNT odors, and C-4 odors, respectively. Field studies with detector dogs have demonstrated possible candidates for new pseudo scents as well as the potential use of controlled permeation devices as non-hazardous training aids providing consistent permeation of target odors.
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Lung and breast cancers are leading causes of cancer death worldwide. Prior exploratory work has shown that patterns of biochemical markers have been found in the exhaled breath of patients with lung and breast cancers that are distinguishable from those of controls. However, chemical analysis of exhaled breath has not shown suitability for individual clinical diagnosis. The authors used a food reward-based method of training 5 ordinary household dogs to distinguish, by scent alone, exhaled breath samples of 55 lung and 31 breast cancer patients from those of 83 healthy controls. A correct indication of cancer samples by the dogs was sitting/lying in front of the sample. A correct response to control samples was to ignore the sample. The authors first trained the dogs in a 3-phase sequential process with gradually increasing levels of challenge. Once trained, the dogs' ability to distinguish cancer patients from controls was then tested using breath samples from subjects not previously encountered by the dogs. The researchers blinded both dog handlers and experimental observers to the identity of breath samples. The diagnostic accuracy data reported were obtained solely from the dogs' sniffing, in double-blinded conditions, of these breath samples obtained from subjects not previously encountered by the dogs during the training period. Among lung cancer patients and controls, overall sensitivity of canine scent detection compared to biopsy-confirmed conventional diagnosis was 0.99 (95% confidence interval [CI], 0.99, 1.00) and overall specificity 0.99 (95% CI, 0.96, 1.00). Among breast cancer patients and controls, sensitivity was 0.88 (95% CI, 0.75, 1.00) and specificity 0.98 (95% CI, 0.90, 0.99). Sensitivity and specificity were remarkably similar across all 4 stages of both diseases. Training was efficient and cancer identification was accurate; in a matter of weeks, ordinary household dogs with only basic behavioral "puppy training" were trained to accurately distinguish breath samples of lung and breast cancer patients from those of controls. This pilot work using canine scent detection demonstrates the validity of using a biological system to examine exhaled breath in the diagnostic identification of lung and breast cancers. Future work should closely examine the chemistry of exhaled breath to identify which chemical compounds can most accurately identify the presence of cancer.
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Lung cancer is a leading cause of cancer death, with the prognosis adversely affected by late diagnosis. Early diagnosis of lung cancer is desirable, but current evidence does not support the application of screening with techniques such as chest radiography, sputum cytology or computed tomography. Breath analysis, which includes gaseous phase analysis that measures volatile organic compounds using electronic noses, exhaled nitric oxide, and exhaled breath condensate (EBC), has been proposed as a non-invasive and simple technique to investigate neoplastic processes in the airways. EBC can be easily collected by breathing into a cooling system that condenses the water vapour in the breath. EBC has already been demonstrated to be useful in investigating inflammatory and oxidative stress changes in various respiratory conditions as it contains measurable mediators of airway inflammation and oxidative stress markers. Furthermore, EBC has also been shown to be a useful method to monitor severity of diseases such as asthma and to act as a surrogate measure of compliance to medical therapy. Presently, there still remains a relative paucity of lung cancer research involving EBC. However, since EBC is a simple, non-invasive technique that can be easily performed, even in ill patients, it has the potential to be validated for use in screening for the early diagnosis of lung cancer.
Chapter
Breath tests date from the earliest history of medicine because physicians in ancient times knew that the odor of the breath is altered in some diseases (1). Even today the astute physician uses his or her nose to supplement sight, sound, and touch at the patient’s bedside. Some breath aromas are highly characteristic of disease: patients with diabetic ketoacidosis smell like rotting apples, mainly due to acetonemia. Chronic renal failure causes the breath to smell like stale urine, due to increased levels of dimethylamine and trimethylamine in the blood, and advanced liver failure causes the musty stench of “fetor hepaticus.” A patient with a lung abscess may smell like a sewer because of the proliferation of anaerobic bacteria, and indulgence in tobacco, alcohol, garlic, or curry each leaves its own distinctive olfactory signature in the breath.
Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.
Article
While low-dose CT scans have been shown to detect greater numbers of early lung cancers than conventional CXR, the first randomized trial of CT versus CXR screening in more than 50 000 subjects has shown a 20% reduction in mortality with CT. There are several other randomized trials in progress. CT scanning may be a useful technique for identifying lung cancer at an earlier stage and may reduce mortality. However, before it can be used on a wider scale, issues such as overdiagnosis bias, cost-effectiveness, false positive findings of multiple noncalcified nodules and the willingness of the relevant population to accept CT scanning need to be evaluated. There is still very little information on the cost per life-year saved as a result of CT scanning, as the data to date is very imprecise. There is no evidence that screening programs influence smoking rates despite the inclusion of cessation programs in many trials. Furthermore, if CT screening is adopted, much work is needed to persuade individuals at high risk, mostly current or former heavy smokers with some airflow obstruction, to participate in a screening program.
Article
Malignant Pleural Mesothelioma (MPM) is a tumour of the surface cells of the pleura that is highly aggressive and mainly caused by asbestos exposure. Electronic noses capture the spectrum of exhaled volatile organic compounds (VOCs) providing a composite biomarker profile (breathprint). We tested the hypothesis that an electronic nose can discriminate exhaled air of patients with MPM from subjects with a similar long-term professional exposure to asbestos without MPM and from healthy controls. 13 patients with a histology confirmed diagnosis of MPM (age 60.9±12.2 year), 13 subjects with certified, long-term professional asbestos exposure (age 67.2±9.8), and 13 healthy subjects without asbestos exposure (age 52.2±16.2) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by an electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validated accuracy (CVA) was calculated. Breathprints from patients with MPM were separated from subjects with asbestos exposure (CVA: 80.8%, sensitivity 92.3%, specificity 85.7%). MPM was also distinguished from healthy controls (CVA: 84.6%). Repeated measurements confirmed these results. Molecular pattern recognition of exhaled breath can correctly distinguish patients with MPM from subjects with similar occupational asbestos exposure without MPM and from healthy controls. This suggests that breathprints obtained by electronic nose have diagnostic potential for MPM.
Article
Volatiles organic compounds (VOCs) in urine have been proposed as cancer biomarkers. To evaluate the efficacy of prostate cancer (PCa) detection by trained dogs on human urine samples. A Belgian Malinois shepherd was trained by the clicker training method (operant conditioning) to scent and recognize urine of people having PCa. All urine samples were frozen for preservation and heated to the same temperature for all tests. After a learning phase and a training period of 24 mo, the dog's ability to discriminate PCa and control urine was tested in a double-blind procedure. Urine was obtained from 66 patients referred to a urologist for elevated prostate-specific antigen or abnormal digital rectal examination. All patients underwent prostate biopsy and two groups were considered: 33 patients with cancer and 33 controls presenting negative biopsies. During each "run," the dog was asked to signal a cancer urine among six samples containing only one cancer urine and five randomly selected controls. Sensitivity and specificity of the test were assessed. The dog completed all the runs and correctly designated the cancer samples in 30 of 33 cases. Of the three cases wrongly classified as cancer, one patient was rebiopsied and a PCa was diagnosed. The sensitivity and specificity were both 91%. This study shows that dogs can be trained to detect PCa by smelling urine with a significant success rate. It suggests that PCa gives an odor signature to urine. Identification of the VOCs involved could lead to a potentially useful screening tool for PCa.
Article
The use of gas sensor arrays as medical diagnosis instruments has been proposed several years ago. Since then, the idea has been proven for a limited number of diseases. The case of lung cancer is particularly interesting because it is supported by studies that have shown the correlation between the composition of breath and the disease. However, it is known that many other diseases can alter the breath composition, so for lung cancer diagnosis it is necessary not only to detect generic alterations but those specifically consequent to cancer. In this paper an experiment, performed in the bronchoscopy unit of a large hospital, aimed at discriminating between lung cancer, diverse lung diseases and reference controls is illustrated. Results show not only a satisfactory identification rate of lung cancer subjects but also a non-negligible sensitivity to breath modification induced by other affections. Furthermore, the effects of some compounds frequently found in the breath of lung cancer subjects have also been studied. Results indicate that breath samples of control individuals drift towards the lung cancer group when added with either single or mixtures of these alleged cancer-related compounds.
Article
A sensor consisting of an array of gold nanoparticles can distinguish the breath of lung cancer patients from the breath of healthy individuals without the need to pre-treat or dehumidify the samples.
Article
Lung cancer is the leading cause of cancer death. Results of therapeutic interventions are particularly discouraging when the disease is discovered in an advanced stage. Early diagnosis is limited by the fact that the disease usually develops asymptomatically and available screening methods do not fulfil the requirements for reliable discrimination between patients with lung cancer and subjects not suffering from the disease. Breath sampling is completely noninvasive and provides a potentially useful approach to screening lung cancer. Exhaled biomarkers contain both volatile and nonvolatile molecules. The profile of volatile organic compounds is different in patients with lung cancer than in control subjects. In exhaled breath condensate, the proteomic profile of breath from cancer patients differs from that of healthy smokers. We reviewed the scientific evidence demonstrating that a unique chemical signature can be detected in the breath of patients with lung cancer and that the exhaled breath biomarker profile could aid clinical decision making.
Article
Given the reports made about dogs detecting cancer on the basis of odour, our hypothesis is that the volatile organic compounds produced by tumours, and detected by dogs, are products of MHC genes. Two lines of evidences support this hypothesis: (1) human body odour is genetically determined by MHC. These antigen molecules (HLA in humans) have soluble and detectable isoforms that are present in body fluids such as blood, urine and sweat; (2) there is a strong association between changes in HLA expression and cancer. Tumour transformation is frequently associated with low classical HLA class I molecules expression, namely HLA-A, HLA-B, and HLA-C. In addition, cancer is associated with high nonclassical HLA class I molecules expression, such as HLA-G and HLA-E. These evidences suggest that these HLA-associated olfactory cues of human cancer could be easily analysed, for example, by the "electronic nose", making possible a very precocious and reliable diagnostic of cancer. Because cancer immunescape mechanism is similar to that observed in the materno-fetal immune tolerance, we propose also that immunomodulatory abortifacients could be a good strategy in cancer treatment.
Article
The objective of this study was to summarize the published literature concerning the epidemiology of lung cancer. A narrative review of published evidence was conducted, identifying and summarizing key reports that describe the occurrence of lung cancer in populations and factors that affect lung cancer risk. In the United States, lung cancer remains the leading cause of cancer death in both men and women, even though an extensive list of modifiable risk factors has long been identified. The predominant cause of lung cancer is exposure to tobacco smoke, with active smoking causing most cases but passive smoking also contributing to the lung cancer burden. The reductions in smoking prevalence in men that occurred in the late 1960s through the 1980s will continue to drive lung cancer mortality rates downward in men during the first portion of this century, but rates in women have not yet begun to decrease. Fortunately, exposures to major occupational respiratory carcinogens have largely been controlled, but the population is still exposed to environmental causes of lung cancer, including radon, the second leading cause of lung cancer death.
Article
Volatile organic compounds are able to be detected in the exhaled breath by a variety of sensing techniques. These volatiles may be produced by cellular metabolic processes, or inhaled/absorbed from exogenous sources. Lung cancer cells may produce and process these compounds different than normal cells. The differences may be detectable in the breath. The following manuscript will review the evidence supporting the premise that a unique chemical signature can be detected in the breath of patients with lung cancer, discuss the results of studies using mass spectrometry and nonspecific chemical sensing techniques to detect the unique lung cancer signature, and speculate on the advancements that must occur to develop a breath test accurate enough to be clinically useful.
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