Alternative Test Research Articles

Multi-Endpoint Acute Toxicity Assessment of Organic Compounds Using Large-Scale Machine Learning Modeling.

In recent years, alternative animal testing methods such as computational and machine learning approaches have become increasingly crucial for toxicity testing. However, the complexity and scarcity of available biomedical data challenge the development of predictive models. Combining nonlinear machine learning together with multicondition descriptors offers a solution for using data from various assays to create a robust model. This work applies multicondition descriptors (MCDs) to develop a QSTR (Quantitative Structure-Toxicity Relationship) model based on a large toxicity data set comprising more than 80,000 compounds and 59 different end points (122,572 data points). The prediction capabilities of developed single-task multi-end point machine learning models as well as a novel data analysis approach with the use of Convolutional Neural Networks (CNN) are discussed. The results show that using MCDs significantly improves the model and using them with CNN-1D yields the best result (R2train = 0.93, R2ext = 0.70). Several structural features showed a high level of contribution to the toxicity, including van der Waals surface area (VSA), number of nitrogen-containing fragments (nN+), presence of S-P fragments, ionization potential, and presence of C-N fragments. The developed models can be very useful tools to predict the toxicity of various compounds under different conditions, enabling quick toxicity assessment of new compounds.

Assessment of skin sensitization potential of zinc oxide, aluminum oxide, manganese oxide, and copper oxide nanoparticles through the local lymph node assay: 5-bromo-deoxyuridine flow cytometry method

ABSTRACT The advent of nanotechnology has significantly spurred the utilization of nanoparticles (NPs) across diverse sectors encompassing industry, agriculture, engineering, cosmetics, and medicine. Metallic oxides including zinc oxide (ZnO), copper oxide (CuO), manganese oxide (Mn2O3), and aluminum oxide (Al2O3), in their NP forms, have become prevalent in cosmetics and various dermal products. Despite the expanding consideration of these compounds for dermal applications, their potential for initiating skin sensitization (SS) has not been comprehensively examined. An in vivo assay, local lymph node assay: 5-bromo-2-deoxyuridine-flow cytometry method (LLNA: BrdU-FCM) recognized as an alternative testing method for screening SS potential was used to address these issues. Following the OECD TG 442B guidelines, NPs suspensions smaller than 50 nm size were prepared for ZnO and Al2O3 at concentrations of 10, 25, and 50%, and Mn2O3 and CuO at concentrations of 5, 10, and 25%, and applied to the dorsum of each ear of female BALB/c mice on a daily basis for 3 consecutive days. Regarding the prediction of test substance to skin sensitizer if sensitization index (SI)≥2.7, all 4 NPs were classified as non-sensitizing. The SI values were below 2.06, 1.33, 1.42, and 0.99 for ZnO, Al2O3, Mn2O3, and CuO, respectively, at all test concentrations. Although data presented were negative with respect to adverse SS potential for these 4 NPs, further confirmatory tests addressing other key events associated with SS adverse outcome pathway need to be carried out to arrive at an acceptable conclusion on the skin safety for both cosmetic and dermal applications.

Guidelines for Manufacturing and Application of Organoids: Skin.

To address the limitations of animal testing, scientific research is increasingly focused on developing alternative testing methods. These alternative tests utilize cells or tissues derived from animals or humans for in vitro testing, as well as artificial tissues and organoids. In western countries, animal testing for cosmetics has been banned, leading to the adoption of artificial skin for toxicity evaluation, such as skin corrosion and irritation assessments. Standard guidelines for skin organoid technology becomes necessary to ensure consistent data and evaluation in replacing animal testing with in vitro methods. These guidelines encompass aspects such as cell sourcing, culture techniques, quality requirements and assessment, storage and preservation, and organoid-based assays.

The HDI + ROPE decision rule is logically incoherent but we can fix it.

The Bayesian highest-density interval plus region of practical equivalence (HDI + ROPE) decision rule is an increasingly common approach to testing null parameter values. The decision procedure involves a comparison between a posterior highest-density interval (HDI) and a prespecified region of practical equivalence. One then accepts or rejects the null parameter value depending on the overlap (or lack thereof) between these intervals. Here, we demonstrate, both theoretically and through examples, that this procedure is logically incoherent. Because the HDI is not transformation invariant, the ultimate inferential decision depends on statistically arbitrary and scientifically irrelevant properties of the statistical model. The incoherence arises from a common confusion between probability density and probability proper. The HDI + ROPE procedure relies on characterizing posterior densities as opposed to being based directly on probability. We conclude with recommendations for alternative Bayesian testing procedures that do not exhibit this pathology and provide a "quick fix" in the form of quantile intervals. This article is the work of the authors and is reformatted from the original, which was published under a CC-BY Attribution 4.0 International license and is available at https://psyarxiv.com/5p2qt/. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Guidelines for Manufacturing and Application of Organoids: Lung.

The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.

Men’s perceptions of HIV self-testing in Eswatini: a qualitative study

ABSTRACT Men in Eswatini test for HIV at lower rates compared to women despite the widespread availability of HIV testing services in the country. HIV self-test kits have been proposed as an HIV testing model to reach more men by bypassing the health facility, which is known to be a barrier for men using HIV testing services. In this study, we sought to understand men’s perspectives on HIV self-testing in Eswatini. We conducted semi-structured interviews with 22 men, recruited from a rural community and from an urban men’s clinic, to assess their awareness of HIV self-testing and their perceptions of it as an alternative HIV testing option. Findings show that men were aware of HIV self-testing but had concerns that left most feeling hesitant about adopting it. Many men expressed doubts about the accuracy of self-testing and their own technical competence to use the kit without supervision. They also expressed fears about testing, and possibly learning they were HIV positive, without adequate pre – and post-HIV test counseling. To allay men’s fears and improve uptake of HIV self-testing, practitioners might consider innovative methods such as virtual counseling services and linking HIV self-testing to other community-based HIV care services.

Ocular vestibular evoked myogenic potentials in different types of amblyopia

ABSTRACT Clinical relevance The visual system plays an important role in the development of the vestibular-ocular reflex (VOR). In clinical practice, the ocular vestibular evoked myogenic potential (oVEMP) test is used to assess contralateral VOR. Background This study sought to compare the oVEMP in patients with anisometropic, strabismic, and mixed amblyopia using unilateral and bilateral (simultaneous binaural) stimulation. Methods Forty-two amblyopic patients (20 males and 22 females) with a mean age of 10.48 ± 4.00 years (range: 5 – 20 years) were examined. The Titmus stereopsis test, alternate cover test, and best-corrected visual acuity were evaluated. Patients were divided into three groups: anisometropic, strabismic, and mixed amblyopia. The oVEMP responses including the amplitude of electrical activity (n1-p1 complex) and the latencies (n1 and p1) of the VOR responses were recorded under unilateral and bilateral stimulations. Results In the anisometropic and strabismic group, n1 latency was significantly faster in the non-amblyopic eyes compared to amblyopic eyes (Z = −2.04, p = 0.042, andZ = −2.54, p = 0.024 respectively). Mean p1 latency was significantly faster in the non-amblyopic eyes compared to the amblyopic eyes of the strabismic group (Z = −2.31, p = 0.011)In all groups, the p1 latency was faster in the non-amblyopic eye compared to bilateral stimulation (all, p < 0.05). In all groups, the n1-p1 amplitude was not significantly different between the two eyes, and between each eye and bilateral stimulation (all, p > 0.05). No significant correlation was found between the depth of amblyopia and n1 and p1 responses (all, p > 0.05). In all groups there was no significant difference in the latency of n1 and p1 between the amblyopic eye and bilateral stimulation (all, p > 0.05). Conclusion Regardless of its type, amblyopia affects vestibular-ocular reflex responses. Further research is warranted to clarify the effect of the disease and its treatment on the ocular-vestibular system.

MDPV (3,4-methylenedioxypyrovalerone) administered to mice during development of the central nervous system produces persistent learning and memory impairments

BackgroundSynthetic cathinones (SC) constitute the second most frequently abused class of new psychoactive substances. They serve as an alternative to classic psychostimulatory drugs of abuse, such as methamphetamine, cocaine, or 3,4-methylenedioxymethamphetamine (MDMA). Despite the worldwide prevalence of SC, little is known about their long-term impact on the central nervous system. Here, we examined the effects of repeated exposure of mice during infancy, to 3,4-methylenedioxypyrovalerone (MDPV), a SC potently enhancing dopaminergic neurotransmission, on learning and memory in young adult mice.MethodsAll experiments were performed on C57BL/6J male and female mice. Animals were injected with MDPV (10 or 20 mg/kg) and BrdU (bromodeoxyuridine, 25 mg/kg) during postnatal days 11–20, which is a crucial period for the development of their hippocampus. At the age of 12 weeks, mice underwent an assessment of various types of memory using a battery of behavioral tests. Afterward, their brains were removed for detection of BrdU-positive cells in the dentate gyrus of the hippocampal formation with immunohistochemistry, and for measurement of the expression of synaptic proteins, such as synaptophysin and PSD95, in the hippocampus using Western blot.ResultsExposure to MDPV resulted in impairment of spatial working memory assessed with Y-maze spontaneous alternation test, and of object recognition memory. However, no deficits in hippocampus-dependent spatial learning and memory were found using the Morris water maze paradigm. Consistently, hippocampal neurogenesis and synaptogenesis were not interrupted. All observed MDPV effects were sex-independent.ConclusionsMDPV administered repeatedly to mice during infancy causes learning and memory deficits that persist into adulthood but are not related to aberrant hippocampal development.

Performance of modified colistin broth disc elution vis-a-vis broth microdilution method for susceptibility testing of Enterobacterales

Performance of modified colistin broth disc elution vis-a-vis broth microdilution method for susceptibility testing of <i>Enterobacterales</i>

Randomized, crossover trial: comparing the effects of standardized egg-white meal and Vital® on global gastric emptying parameters and intragastric meal distribution in healthy Asian participants.

Measurements of gastric emptying and accommodation for alternative test-meal protocol during gastric emptying scintigraphy (GES), such as high-calorie nutrient drinks, are not fully established. We aimed to compare the effects of standardized egg-white meal (EWM) versus high-calorie nutrient drink (Vital®; Abbott Laboratories) on global GES parameters and intragastric meal distribution at immediate scan (IMD0h). Of 84 screened participants, 60 asymptomatic healthy Asian population (38 females; 24.0±1.5years; 23.8±2.6kg/m2) were recruited in this 2×2 (AB/BA) crossover trial. Participants were randomized to a 4-h GES with 99mTc-radiolabeled EWM (~255.8kcal), followed by a 200mL Vital® (300kcal), or vice versa, separated by a 2-week washout period. Global meal retention (GMR), power-exponential model emptying parameters (half-emptying [T1/2], lag phases [Tlag2%, Tlag5%, Tlag10%]), and IMD0h were determined and compared. GMRs for both test meals were within the international standard references for solid GES. Compared to EWM, Vital® exhibited significantly lower GMRs (faster emptying) from 0.5 to 3h (all P<0.001) but comparable at 4h (P=0.153). Similar observations were found for the model-based T1/2 and the different Tlag thresholds (all P<0.001). Furthermore, IMD0h was found to be lower with Vital®, indicating lower gastric accommodation (faster antral filling) immediately post-ingestion (P<0.001). Both test meals showed significant moderate-to-strong positive associations at the late-phase GE (GMR 2-4h, T1/2) (all P<0.05). Overall, Vital® is an acceptable alternative test meal to the EWM for GES; however, exercise caution when interpreting early-phase GE. The normative values for global GES parameters and IMD0h are also established.

Climate vulnerability and child health outcomes in developing countries: Do women's political empowerment and female education make the difference?

Health as a common good is of paramount importance for the world, especially in developing countries. This paper contributes to the literature by analysing the effect of climate vulnerability on child health outcomes in a sample of 107 developing countries over the period 2000–2020. We also analyse the mediating role of women's political empowerment and women's education in the relationship between climate vulnerability and child health outcomes. Using the method of generalised moments in a two-stage system and linear regression absorbing several levels of fixed effects, we found robust evidence that climate vulnerability worsens child health outcomes. We also found that women's political empowerment (WPE) and women's education mitigate the negative effect of climate vulnerability on child health outcomes. These results remain robust against several alternative tests and therefore highlight the need to better examine how the health consequences of climate vulnerability are structured by gender in developing countries. Given the importance of women as agents of change, it would be more beneficial for policymakers to include them in the decision-making process.

The Relationship Between Potassium And Ureum Levels Of New Drugs In Drug Resistant Tuberculosis Patients

The use of new types of drugs in RO TB patients will cause disturbances in the body's electrolytes, especially potassium levels, as well as disturbances in urea levels caused by the excretion of urea that is retained in the body. Continuous increases in urea in the body result in the kidneys not being able to work optimally. The aim of this study was to determine the relationship between potassium levels and urea levels on new types of drugs in RO TB patients. The research method used is analytical observational with a cross sectional approach. This research was conducted on 16 February – 16 March 2023 with research subjects being RO TB patients who received treatment with a new type of drug at the Lung Hospital dr. Ario Wirawan Salatiga as many as 21 respondents using a sampling technique that is the total population. Potassium levels were measured using the ISE (Ion Selective Electrode) method and urea levels used the enzymatic UV test method. The data was then processed using the Shapiro-Wilk normality test, then continued with prerequisite tests (crosstab test and homogeneity test) then continued with hypothesis testing, because my data scale was ratio and nominal, the alternative test used was the Chi-Square Test. The equipment test results obtained a homogeneity test with a P value of 0.698 and 0.610 (0.05), meaning the data was homogeneous. The test results for the relationship between potassium and urea levels on new types of drugs for RO TB patients were Chi-Square hypothesis test results with a P value of 0.152 and 0.384 ( 0.05) means there is no relationship between potassium levels and urea levels on new types of drugs in RO TB patients. The results show that the TB drugs bedaquiline and delamanid do not cause kidney function disorders so that RO TB patients can consume these TB drugs regularly.

Ventral hippocampus mediates inter-trial responding in signaled active avoidance

The hippocampus has a central role in regulating contextual processes in memory. We have shown that pharmacological inactivation of ventral hippocampus (VH) attenuates the context-dependence of signaled active avoidance (SAA) in rats. Here, we explore whether the VH mediates intertrial responses (ITRs), which are putative unreinforced avoidance responses that occur between trials. First, we examined whether VH inactivation would affect ITRs. Male rats underwent SAA training and subsequently received intra-VH infusions of saline or muscimol before retrieval tests in the training context. Rats that received muscimol performed significantly fewer ITRs, but equivalent avoidance responses, compared to controls. Next, we asked whether chemogenetic VH activation would increase ITR vigor. In male and female rats expressing excitatory (hM3Dq) DREADDs, systemic CNO administration produced a robust ITR increase that was not due to nonspecific locomotor effects. Then, we examined whether chemogenetic VH activation potentiated ITRs in an alternate (non-training) test context and found it did. Finally, to determine if context-US associations mediate ITRs, we exposed rats to the training context for three days after SAA training to extinguish the context. Rats submitted to context extinction did not show a reliable decrease in ITRs during a retrieval test, suggesting that context-US associations are not responsible for ITRs. Collectively, these results reveal an important role for the VH in context-dependent ITRs during SAA. Further work is required to explore the neural circuits and associative basis for these responses, which may be underlie pathological avoidance that occurs in humans after threat has passed.

A Modified Frailty Phenotype Used for Identifying Frailty in Health Care Practice: Validation Among Chinese Older Adults

ObjectivesThe study aimed to evaluate a simplified and practical frailty detection tool derived from the Fried frailty phenotype (FFP). This tool was developed to facilitate the identification of frail individuals in constrained settings, addressing the challenges posed by uncertain cutoffs of FFP indicators in prompt frailty assessment. DesignA longitudinal study and a cross-sectional study. Settings and ParticipantsA total of 1978 older adults aged 67.4 ± 6.16 years from the China Health and Retirement Longitudinal Study (CHARLS), and 972 older adults aged 72.8 ± 6.75 years from a pilot cross-sectional study conducted in Shanghai communities. MethodsFrailty was assessed according to the FFP criterion. A Chinese modified frailty phenotype (CMFP) was developed, incorporating specific cutoffs for grip strength and an alternative test for walk speed. The internal consistency reliability, the criterion, and predictive validity of the CMFP were evaluated. ResultsThe 5-time chair stand test (5t-CST) was significantly associated with the 2.5-m walk test (r = 0.373 in the CHARLS and 0.423 in the pilot study). Each element of the CMFP showed moderate to strong correlations with the total CMFP score and showed Cronbach's alpha of 0.303 and 0.358 in both populations. The Spearman's r and kappa values between the CMFP and the FFP were 0.795 and 0.663 in the CHARLS, and 0.676 and 0.537 in the pilot study. The areas under the curve (AUC) were 0.936 and 0.928 in the 2 studies, respectively. In addition, frailty assessed by the CMFP significantly predicted future incidence of outcomes, including all-cause mortality, activities of daily living (ADL)/instrumental ADL disability, hospitalization, and depression. Conclusions and ImplicationsThe study demonstrated the CMFP as a valid tool, particularly highlighting its excellent predictive ability on outcomes. The 5t-CST may act as a viable alternative test for assessing slowness. The CMFP can be systematically integrated into preclinical practice to identify frail individuals, especially within constrained spaces.

Complication rates associated with nasoesophageal versus nasogastric feeding tube placement in dogs and cats: a randomised controlled trial.

To determine the rate of accidental placement of nasoenteric tubes into the respiratory tract. To compare the methods of checking correct tube placement. To compare the complication rates between nasoesophageal and nasogastric tubes. Animals requiring nasoenteric feeding tubes were prospectively randomised to have either nasoesophageal or nasogastric tube placement. Various techniques for assessing tube position were compared with thoracic radiographic findings. Complications during placement and use were recorded. Ninety-seven animals (82 dogs and 15 cats) were studied. The tube was misplaced into the respiratory tract in three (3.1%) cases. No technique for checking placement was completely concordant with radiography but the presence of negative pressure at the thoracic inlet during placement was consistent with the presence of the tube in the oesophagus in 86.2% cases, while capnography can be considered to confirm tracheal placement. The overall rate of complications during tube placement was 25.8%, with mostly minor clinical complications reported. There was no significant difference in the new-onset regurgitation/vomiting rate, or complications while the tube was insitu between the nasoesophageal and nasogastric groups. Misplacement of nasoenteric tubes is uncommon but a consistent alternative test to radiography for checking correct nasoenteric tube placement was not demonstrated. The choice of placement of either a nasoesophageal or nasogastric tube should be guided by clinician preference, and clients should be warned about possible complications during placement and while the nasoenteric tube is insitu.

Mast cell versus basophil activation test in allergy: Current status.

In the past two decades, we witnessed the evolution of the basophil activation test (BAT) from mainly research applications to a potential complementary diagnostic tool to document IgE-dependent allergies. However, BAT presents some technical weaknesses. Around 10%-15% of tested patients are non-responders, BAT can be negative immediately post-reaction and the use of fresh basophils, ideally analysed within 4 h of collection, restricts the number of tests that can be performed per sample. The need for fresh basophils is especially limiting when conducting batch analyses and interlaboratory comparisons to harmonize BAT methodology. These limitations significantly hinder the wider application of BAT and urge the development of alternative testing, such as the mast cell activation test (MAT). The essential difference between BAT and MAT is the heterogeneity of the starting material used to perform the assays. Mast cells are tissue-resident, so cannot be easily accessed. Current alternative sources for functional studies are generating primary human mast cells, differentiated from donor progenitor cells, or using immortalized mast cell lines. Hence, the methodological approaches for MAT are not only vastly different from BAT, but also different among MAT protocols. This review summarizes the advantages and disadvantages of BAT and MAT assays, dedicating special attention to elucidating the key differences between the cellular sources used and provides an overview of studies hitherto performed comparing BAT and MAT in the diagnosis of IgE-mediated food and drug allergies.

Shabbat and Shattered Dreams: Religious Accommodations for Public Exams in South Korea

Abstract Today in South Korea, individuals of certain faiths are unable to take a wide range of state-administered qualifying examinations due to their religious convictions. The Constitutional Court of Korea has repeatedly refused their request for religious accommodations, such as an alternative test date for Sabbath or holy day observers who are unable to take exams on their original dates. The authors analyze the series of Constitutional Court decisions rejecting the need for such accommodation by focusing on the court’s use of its main analytical tool, the proportionality principle. These decisions reveal important shortcomings in the court’s application of the proportionality principle, including challenges inherent to proportionality and more specific deficiencies in the court’s application of the general principle. The article thus sheds light on how the proportionality principle is applied in the context of Korean constitutional jurisprudence and the resultant deprivation of protection for certain fundamental rights in Korea. The authors compare the court’s approach with that of courts in Spain, Switzerland, and the United States. They then propose a number of ways to improve the court’s proportionality analysis and its constitutional reasoning.

Do export responses to exchange rate movements differ in micro export flows?

This paper empirically examines how exports respond to exchange rate movements (exchange rate and exchange rate volatility) at the micro and macro levels using Turkey’s bilateral export data with 65 partner countries. Panel data contaninig 65 cross-sectional dimensions and 60 monthly time series dimensions from 2018:01 to 2022:12 are used. The empirical results of the Poisson Pseudo Maximum Likelihood (PPML) technique show that the negative effect of exchange rate volatility on micro export flows is amplified. Moreover, the potential positive effect of the exchange rate on micro export flows is weaker. Our findings are robust against the alternative method of exchange rate volatility and nominal exchange rate volatility. Our results are also intact under alternative robustness tests. The paper provides notable policy implications. Policymakers should be aware of the potential structural differences between micro and macro exports. Therefore, policymakers should also consider other aspects such as cross-border e-commerce when formulating economic policies on microexports.

KoCVAM-led development of phototoxicity alternative test method using reconstructed human epidermis model (KeraSkin™)

Phototoxicity is an acute toxic reaction induced by topical skin exposure to photoreactive chemicals followed by exposure to environmental light and thus chemicals that absorb UV are recommended to be evaluated for phototoxic potential. There are currently three internationally harmonized alternative test methods for phototoxicity. One of them is the in vitro Phototoxicity: RhE Phototoxicity test method (OECD TG498).Korean center for the Validation of Alternative Methods (KoCVAM) developed an in vitro phototoxicity test method using a KeraSkin™ reconstructed human epidermis model (KeraSkin™ Phototoxicity Assay) as a ‘me-too’ test method of OECD TG498.For the development and optimization of KeraSkin™ Phototoxicity Assay, the following test chemicals were used: 6 proficiency chemicals in OECD TG498 (3 phototoxic and 3 non-phototoxic), 6 reference chemicals in OECD Performance Standard No. 356 (excluding the proficiency test chemicals, 3 phototoxic and 3 non-phototoxic) and 13 additional chemicals (7 phototoxic and 6 non-phototoxic). Based on the test results generated from the test chemicals above, the overall predictive capacity of KeraSkin™ Phototoxicity Assay was calculated. In particular, the assay exhibited 100 % accuracy, 100 % sensitivity, and 100 % specificity. Therefore, it fulfills the requirements to be included as a ‘me-too’ test method in OECD TG498.

Diagnosis and Severity Assessment of COPD Using a Novel Fast-Response Capnometer and Interpretable Machine Learning

Introduction Spirometry is the gold standard for COPD diagnosis and severity determination, but is technique-dependent, nonspecific, and requires administration by a trained healthcare professional. There is a need for a fast, reliable, and precise alternative diagnostic test. This study’s aim was to use interpretable machine learning to diagnose COPD and assess severity using 75-second carbon dioxide (CO2) breath records captured with TidalSense’s N-TidalTM capnometer. Method For COPD diagnosis, machine learning algorithms were trained and evaluated on 294 COPD (including GOLD stages 1–4) and 705 non-COPD participants. A logistic regression model was also trained to distinguish GOLD 1 from GOLD 4 COPD with the output probability used as an index of severity. Results The best diagnostic model achieved an AUROC of 0.890, sensitivity of 0.771, specificity of 0.850 and positive predictive value (PPV) of 0.834. Evaluating performance on all test capnograms that were confidently ruled in or out yielded PPV of 0.930 and NPV of 0.890. The severity determination model yielded an AUROC of 0.980, sensitivity of 0.958, specificity of 0.961 and PPV of 0.958 in distinguishing GOLD 1 from GOLD 4. Output probabilities from the severity determination model produced a correlation of 0.71 with percentage predicted FEV1. Conclusion The N-TidalTM device could be used alongside interpretable machine learning as an accurate, point-of-care diagnostic test for COPD, particularly in primary care as a rapid rule-in or rule-out test. N-TidalTM also could be effective in monitoring disease progression, providing a possible alternative to spirometry for disease monitoring.