Cluster Analysis of Allergic Poly-Sensitizations in Urban Adults with Asthma

Introduction While reliable, quantitative in vitro testing for sensitivity to aeroallergens has been available for decades, if and how asthma severity markers might be predictably expressed in clusters matched for comparable multiple sensitizations is unknown. Objective Our aim is to use machine learning techniques to explore how allergic poly-sensitization (APS) clusters may serve as precision markers in adult urban patients with moderate to severe asthma. Methods We constructed a database of sensitizations to the 25 aeroallergens in the Zone 1 Northeastern US ImmunoCAP® assay. We used the Scikit-Learn® machine learning library to perform model-based clustering to identify APS clusters. Clusters were compared for differences in common clinical markers of asthma. Results The database consisted of 509 patients. Unbiased mixture modeling identified ten clusters of increasing APS of varying size (n = 1 to 339) characterized by significant increases in mean serum immunoglobulin E (p<.001), peripheral blood eosinophil count (p<.001), and DLCO (p=.02). There was a significant decline in mean age at presentation (p<.001), FEV1/FVC (p=.01), and FEF25-75 (p=.002), but not FEV1 (p=.29), nor RV/TLC (p=.14) with increasing APS by simple linear regression. Finally, we identified two divergent paths for the poly-atopic march, one driven by perennial and the other by seasonal allergens. Conclusion We conducted a pilot study for a novel machine learning understanding and approach to the classification of APS and potential influences if included in asthma cluster analyses. The methods used here can be easily applied to other geographic regions with different allergens ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We thank the Margaret Wolf Memorial Pulmonary Research Fund for providing financial support for this research ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research was approved by the Institutional Review Board of the Drexel University College of Medicine who gave ethical approval for this work in an expedited review. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors * APS : Allergic Poly-Sensitization ACO : Asthma-COPD overlap BMI : Body Mass Index CBC : Complete Blood Count CI : Confidence Interval COPD : Chronic Obstructive Pulmonary Disease DLCO : Diffusion Capacity of the Lungs for Carbon Monoxide DPMM : Dirichlet Process Mixture Model D1 : Dermatophagoides pteronyssinus D2 : Dermatophagoides farinae FEF25-75 : Forced expiratory flow at 25–75% of forced vital capacity FEV1 : Volume of air forcibly expired in 1 second FEV1/FVC : Ratio of air forcibly expired in 1 second to the forced vital capacity FVC : Forced Vital Capacity IgE : Immunoglobulin E IQR : Interquartile Range IU/ml : International units per milliliter PCA : Principal Component Analysis PFT : Pulmonary Function Test RV : Residual Volume RV/TLC : Ratio of residual volume to total lung capacity SARP : Severe Asthma Research Program SD : Standard Deviation TLC : Total Lung Capacity VB : Variational Bayes