Rationale: The airway transcriptome includes genes that contribute to the pathophysiologic heterogeneity seen in individuals with asthma.Objectives: We analyzed sputum gene expression for transcriptomic endotypes of asthma (TEA), gene signatures that discriminate phenotypes of disease.Methods: Gene expression in the sputum and blood of patients with asthma was measured using Affymetrix microarrays. Unsupervised clustering analysis based on pathways from the Kyoto Encyclopedia of Genes and Genomes was used to identify TEA clusters. Logistic regression analysis of matched blood samples defined an expression profile in the circulation to determine the TEA cluster assignment in a cohort of children with asthma to replicate clinical phenotypes.Measurements and Main Results: Three TEA clusters were identified. TEA cluster 1 had the most subjects with a history of intubation (P = 0.05), a lower prebronchodilator FEV 1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04) compared with the other TEA clusters. TEA cluster 2, the smallest cluster, had the most subjects that were hospitalized for asthma (P = 0.04). TEA cluster 3, the largest cluster, had normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in children confirmed that TEA clusters 1 and 2 are associated with a history of intubation (P = 5.58 3 10
26) and hospitalization (P = 0.01), respectively.Conclusions: There are common patterns of gene expression in the sputum and blood of children and adults that are associated with near-fatal, severe, and milder asthma.
in the management of subjects with asthma from the young to the very old. In the future, it will be important to develop strategies to prevent the development of asthma and, in children with the disease, to maximize the appropriate use of, and adherence to, the available medications before considering more expensive alternatives. To do this, we will need to standardize and harmonize medical care, while improving communication and setting up systems of collaboration. If executed effectively, this effort should have a marked impact on reducing the prevalence of asthma in the future and the consequent burden of asthma on society.Author disclosures are available with the text of this article at www.atsjournals.org.
ObjectiveTo understand the etiology of tracheotomy‐induced tracheal stenosis by comparing the differences in techniques and mechanical force applied with open tracheotomy (OT) versus percutaneous tracheotomy (PCT) placement.MethodsThis study is an unblinded, experimental, randomized controlled study in an ex‐vivo animal model. Simulated tracheostomies were performed on 10 porcine tracheas, 5 via a tracheal window technique (OT) and 5 using the Ciaglia technique (PCT). The applied weight during the simulated tracheostomy and the compression of the trachea were recorded at set times during the procedure. The applied weight during tracheostomy was used to calculate the tissue force in Newtons. Tracheal compression was measured by anterior–posterior distance compression and as percent change.ResultsAverage forces for scalpel (OT) versus trocar (PCT) were 2.6 N and 12.5 N (p < 0.01), with the dilator (PCT) it was 22.02 N (p < 0.01). The tracheostomy placement with OT required an average force of 10.7 N versus 23.2 N (p < 0.01) with PCT. The average change in AP distance when using the scalpel versus trocar was 21%, and 44% (p < 0.01), with the dilator it was 75% (p < 0.01). The trach placement with OT versus PCT had an average AP distance change of 51% and 83% respectively (p < 0.01).ConclusionThis study demonstrated that PCT required more force and caused more tracheal lumen compression when compared to the OT technique. Based on the increased force required for PCT, we suspect there could also be an increased risk for tracheal cartilage trauma.Level of EvidenceN/A Laryngoscope, 2023
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