Chronic Obstructive Pulmonary Disease (COPD), a major chronic respiratory disease with persistent airflow limitation, is a leading global cause of disability and mortality. Respiratory spirogram time series, routinely collected during pulmonary function tests (PFTs), play a critical role in the early detection of respiratory diseases and in monitoring lung function over time. However, most current AI models for COPD diagnosis are limited to outputting classification results without providing a rationale for their diagnostic process, while current Large Language Models (LLMs) cannot understand spirograms yet, which severely limits their clinical trust and adoption. To tackle this challenge, we leverage a cohort of 234,028 individuals from the UK Biobank (UKB) to propose SpiroLLM, the first multimodal large language model that can understand spirogram. The model extracts morphological features from respiratory curves via a SpiroEncoder and aligns them with PFT numerical values in a unified latent space using a SpiroProjector, ultimately empowering a large language model to generate a comprehensive diagnostic report. Experimental results confirm that SpiroLLM achieved a diagnostic AUROC of 0.8977 (95% CI: 0.88-0.91). In a robustness test with missing core data, it maintained a 100% valid response rate, far surpassing the 13.4% of a text-only model and showcasing the superiority of its multimodal design. This work demonstrates the substantial potential of deeply fusing physiological signals with large language models, establishing a new paradigm for the next generation of interpretable and reliable clinical decision support tools.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition, contributing significantly to global morbidity and mortality. Traditional diagnostic tools are effective in diagnosing COPD. However, these tools demand specialized equipment and expertise. Advances in artificial intelligence (AI) provide a platform for enhancing COPD diagnosis by leveraging diverse data modalities. The existing reviews primarily focus on single modalities and lack information on interpretability and explainability. Thus, this review intends to synthesize the AI-powered frameworks for COPD identification, focusing on data modalities, methodological innovation, evaluation strategies, and reporting limitations and potential biases. By adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was conducted across multiple repositories. From an initial pool of 1978 records, 22 studies were included in this review. The included studies demonstrated exceptional performance in specific settings. Most studies were retrospective and limited in diversity, lacking generalizability and external or prospective validation. This review presents a roadmap for advancing AI-assisted COPD detection. By highlighting the strengths and limitations of existing studies, it supports the development of future research. Future studies can utilize the findings to build models using prospective, multicenter, and multi-ethnic validations, ensuring generalizability and fairness.

Chronic Obstructive Pulmonary Disease (COPD) is a chronic lung condition characterized by airflow obstruction. Current diagnostic methods primarily rely on identifying prominent features in spirometry (Volume-Flow time series) to detect COPD, but they are not adept at predicting future COPD risk based on subtle data patterns. In this study, we introduce a novel deep learning-based approach, DeepSpiro, aimed at the early prediction of future COPD risk. DeepSpiro consists of four key components: SpiroSmoother for stabilizing the Volume-Flow curve, SpiroEncoder for capturing volume variability-pattern through key patches of varying lengths, SpiroExplainer for integrating heterogeneous data and explaining predictions through volume attention, and SpiroPredictor for predicting the disease risk of undiagnosed high-risk patients based on key patch concavity, with prediction horizons of 1-5 years, or even longer. Evaluated on the UK Biobank dataset, DeepSpiro achieved an AUC of 0.8328 for COPD detection and demonstrated strong predictive performance for future COPD risk (p-value < 0.001). In summary, DeepSpiro can effectively predict the long-term progression of COPD disease.

Although high-dimensional clinical data (HDCD) are increasingly available in biobank-scale datasets, their use for genetic discovery remains challenging. Here we introduce an unsupervised deep learning model, Representation Learning for Genetic Discovery on Low-Dimensional Embeddings (REGLE), for discovering associations between genetic variants and HDCD. REGLE leverages variational autoencoders to compute nonlinear disentangled embeddings of HDCD, which become the inputs to genome-wide association studies (GWAS). REGLE can uncover features not captured by existing expert-defined features and enables the creation of accurate disease-specific polygenic risk scores (PRSs) in datasets with very few labeled data. We apply REGLE to perform GWAS on respiratory and circulatory HDCD-spirograms measuring lung function and photoplethysmograms measuring blood volume changes. REGLE replicates known loci while identifying others not previously detected. REGLE are predictive of overall survival, and PRSs constructed from REGLE loci improve disease prediction across multiple biobanks. Overall, REGLE contain clinically relevant information beyond that captured by existing expert-defined features, leading to improved genetic discovery and disease prediction.

Objective. The quality of spirometry manoeuvres is crucial for correctly interpreting the values of spirometry parameters. A fundamental guideline for proper quality assessment is the American Thoracic Society and European Respiratory Society (ATS/ERS) Standards for spirometry, updated in 2019, which describe several start-of-test and end-of-test criteria which can be assessed automatically. However, the spirometry standards also require a visual evaluation of the spirometry curve to determine the spirograms' acceptability or usability. In this study, we present an automatic algorithm based on a convolutional neural network (CNN) for quality assessment of the spirometry curves as an alternative to manual verification performed by specialists.Approach. The algorithm for automatic assessment of spirometry measurements was created using a set of randomly selected 1998 spirograms which met all quantitative criteria defined by ATS/ERS Standards. Each spirogram was annotated as 'confirm' (remaining acceptable or usable status) or 'reject' (change the status to unacceptable) by four pulmonologists, separately for FEV1 and FVC parameters. The database was split into a training (80%) and test set (20%) for developing the CNN classification algorithm. The algorithm was optimised using a cross-validation method.Main results. The accuracy, sensitivity and specificity obtained for the algorithm were 92.6%, 93.1% and 90.0% for FEV1 and 94.1%, 95.6% and 88.3% for FVC, respectively.Significance.The algorithm provides an opportunity to significantly improve the quality of spirometry tests, especially during unsupervised spirometry. It can also serve as an additional tool in clinical trials to quickly assess the quality of a large group of tests.

High-dimensional clinical data are becoming more accessible in biobank-scale datasets. However, effectively utilizing high-dimensional clinical data for genetic discovery remains challenging. Here we introduce a general deep learning-based framework, REpresentation learning for Genetic discovery on Low-dimensional Embeddings (REGLE), for discovering associations between genetic variants and high-dimensional clinical data. REGLE uses convolutional variational autoencoders to compute a non-linear, low-dimensional, disentangled embedding of the data with highly heritable individual components. REGLE can incorporate expert-defined or clinical features and provides a framework to create accurate disease-specific polygenic risk scores (PRS) in datasets which have minimal expert phenotyping. We apply REGLE to both respiratory and circulatory systems: spirograms which measure lung function and photoplethysmograms (PPG) which measure blood volume changes. Genome-wide association studies on REGLE embeddings identify more genome-wide significant loci than existing methods and replicate known loci for both spirograms and PPG, demonstrating the generality of the framework. Furthermore, these embeddings are associated with overall survival. Finally, we construct a set of PRSs that improve predictive performance of asthma, chronic obstructive pulmonary disease, hypertension, and systolic blood pressure in multiple biobanks. Thus, REGLE embeddings can quantify clinically relevant features that are not currently captured in a standardized or automated way.

Spirometry measures lung function by selecting the best of multiple efforts meeting pre-specified quality control (QC), and reporting two key metrics: forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). We hypothesize that discarded submaximal and QC-failing data meaningfully contribute to the prediction of airflow obstruction and all-cause mortality.

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is highly heritable. While COPD is clinically defined by applying thresholds to summary measures of lung function, a quantitative liability score has more power to identify genetic signals. Here we train a deep convolutional neural network on noisy self-reported and International Classification of Diseases labels to predict COPD case-control status from high-dimensional raw spirograms and use the model's predictions as a liability score. The machine-learning-based (ML-based) liability score accurately discriminates COPD cases and controls, and predicts COPD-related hospitalization without any domain-specific knowledge. Moreover, the ML-based liability score is associated with overall survival and exacerbation events. A genome-wide association study on the ML-based liability score replicates existing COPD and lung function loci and also identifies 67 new loci. Lastly, our method provides a general framework to use ML methods and medical-record-based labels that does not require domain knowledge or expert curation to improve disease prediction and genomic discovery for drug design.

Navy divers tend to have large lungs and low expiratory flow rates in the terminal portion of a spirogram. We examined Finnish Navy divers for the presence of air trapping, airway obstruction, and functional airway compression, and their association with lung volumes. Divers (n = 57) and non-diving men (n = 10) underwent a variety of pulmonary function tests. The amount of trapped air was calculated as the subtraction of the total lung capacity (TLC) measured in a single-breath helium dilution test from the TLC in body plethysmography (TLCb). Mean vital capacity (VC) was 6.4 L in the divers versus 5.8 L in the controls (p = 0.006) and TLCb 8.9 L in the divers versus 8.1 L in the controls (p = 0.002). No difference existed between them in the amount of trapped air. However, we found break points in a linear regression model (Davies test) between trapped air and several pulmonary parameters. Those individuals above the break points had lower ratio of forced expiratory volume in first second to forced vital capacity, lower resistance of airways, and higher reactance than those below the break points. In conclusion, navy divers had larger lungs than controls. Large lung volumes (VC >7.31 L or >122% of predicted value) were associated with air trapping. Furthermore, large volumes of air trapping (>1.1 L) were associated with increased residual volume (RV) and RV/TLCb. Despite no concurrent obstruction, functional airway compression, or reduced diffusing capacity, this slowly ventilated trapped air might remain disadvantageous for divers.