Sex differences in sociodemographic, clinical, and laboratory variables in childhood asthma: A birth cohort study.

BACKGROUND: There are marked sex differences in the prevalence and severity of asthma, both during childhood and adulthood. There is a relative lack of comprehensive studies exploring sexdifferences in pediatric asthma cohorts. OBJECTIVE: To identify the most relevant sex differences in sociodemographic, clinical, and laboratory variables in a well-characterized large pediatric asthma cohort. METHODS: We performed a cross-sectional analysis of the Mayo Clinic Olmsted County Birth Cohort. In the full birth cohort, we used a natural language-processing algorithm based on the Predetermined Asthma Criteria for asthma ascertainment. In a stratified random sample of 300 children, we obtained additional pulmonary function tests and laboratory data. We identified the significant sex differences among available sociodemographic, clinical, and laboratory variables. RESULTS: Boys were more frequently diagnosed with having asthma than girls and were younger at the time of asthma diagnosis. There were no sex differences in relation to socioeconomic status. We identified a male predominance in the presence of a tympanostomy tube and a female predominance in the history of pneumonia. A higher percentage of boys had a forced expiratory volume in 1 second/forced vital capacity ratio less than 0.85. Blood eosinophilia and atopic sensitization were also more common in boys. Finally, boys had higher levels of serum periostin than girls. CONCLUSION: This study described significant sex differences in a large pediatric asthma cohort. Overall, boys had earlier and more severe asthma than girls. Differences in blood eosinophilia and serum periostin provide insights into possible mechanisms of the sex bias in childhood asthma.

Urine Mast Cell Mediators in the Evaluation and Diagnosis of Mast Cell Activation Syndrome.

PURPOSE OF REVIEW: Mast cell activation syndrome is defined by severe, episodic, and recurrent symptoms induced by mast cell mediators with objective measurement of increase in biomarkers of mast cell activation and treatment response with mast cell therapies. Increase in serum tryptase from baseline during a mast cell activation episode is currently the most accepted biomarker measurement of mast cell release. However, during symptomatic episodes, serum tryptase can be difficult to obtain as it is a venipuncture procedure. Other objective measures of mast cell activation are needed to complement serum tryptase. RECENT FINDINGS: Urine mast cell mediators can be collected at home and are non-invasive tests. There is emerging evidence for the utility of urine mast cell mediators including histamine, cysteinyl leukotrienes, and prostaglandins in the diagnosis of mast cell activation syndrome. In this review, clinically available urine mast cell mediators will be discussed including N-methylhistamine, leukotriene E4, and 2,3-dinor-11beta-prostaglandin F2 alpha. We discuss the rationale for the use of these urine mast cell mediators and examine the studies analyzing their performance for identifying mast cell activation.

Patient-Centered Practice Guidelines: GRADEing Evidence to Incorporate Certainty, Balance Between Benefits and Harms, Equity, Feasibility, and Cost-Effectiveness.

The practice of medicine in recent years has emphasized the use of evidence-based clinical guidelines to help inform treatment decisions. Since its development in 2004, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach has offered a systematic process for reviewing and summarizing the certainty of evidence found in the medical literature regarding various treatment options. To develop truly patient-centered care guidelines, this appraisal of the certainty of evidence must be combined with an understanding of the balance between benefits and harms, patient preferences, equity, feasibility, cost-effectiveness, and policy implications. This review examines each of these domains in detail, exploring the process and benefits of developing relevant, patient-focused guidelines directly applicable to the practice of modern medicine.

Automated Identification of Aspirin-Exacerbated Respiratory Disease Using Natural Language Processing and Machine Learning: Algorithm Development and Evaluation Study.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an acquired inflammatory condition characterized by the presence of asthma, chronic rhinosinusitis with nasal polyposis, and respiratory hypersensitivity reactions on ingestion of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Despite AERD having a classic constellation of symptoms, the diagnosis is often overlooked, with an average of greater than 10 years between the onset of symptoms and diagnosis of AERD. Without a diagnosis, individuals will lack opportunities to receive effective treatments, such as aspirin desensitization or biologic medications. OBJECTIVE: Our aim was to develop a combined algorithm that integrates both natural language processing (NLP) and machine learning (ML) techniques to identify patients with AERD from an electronic health record (EHR). METHODS: A rule-based decision tree algorithm incorporating NLP-based features was developed using clinical documents from the EHR at Mayo Clinic. From clinical notes, using NLP techniques, 7 features were extracted that included the following: AERD, asthma, NSAID allergy, nasal polyps, chronic sinusitis, elevated urine leukotriene E4 level, and documented no-NSAID allergy. MedTagger was used to extract these 7 features from the unstructured clinical text given a set of keywords and patterns based on the chart review of 2 allergy and immunology experts for AERD. The status of each extracted feature was quantified by assigning the frequency of its occurrence in clinical documents per subject. We optimized the decision tree classifier's hyperparameters cutoff threshold on the training set to determine the representative feature combination to discriminate AERD. We then evaluated the resulting model on the test set. RESULTS: The AERD algorithm, which combines NLP and ML techniques, achieved an area under the receiver operating characteristic curve score, sensitivity, and specificity of 0.86 (95% CI 0.78-0.94), 80.00 (95% CI 70.82-87.33), and 88.00 (95% CI 79.98-93.64) for the test set, respectively. CONCLUSIONS: We developed a promising AERD algorithm that needs further refinement to improve AERD diagnosis. Continued development of NLP and ML technologies has the potential to reduce diagnostic delays for AERD and improve the health of our patients.

Avapritinib versus Placebo in Indolent Systemic Mastocytosis.

BACKGROUND: Indolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM. METHODS: We randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71). The primary end point was mean change in TSS based on the 14-day average of patient-reported severity of 11 symptoms. Secondary end points included reductions in serum tryptase and blood KIT D816V variant allele fraction (≥50%), reductions in TSS (≥50% and ≥30%), reduction in bone marrow mast cells (≥50%), and quality of life measures. RESULTS: From baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003. From baseline to Week 24, 76/141 patients (54%; 45% to 62%) in the avapritinib group compared to 0/71 patients in the placebo group achieved a ≥50% reduction in serum tryptase level; P<0.001. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events. CONCLUSIONS: In this trial, avapritinib was superior to placebo in reducing uncontrolled symptoms and mast-cell burden in patients with ISM. The long-term safety and efficacy of this approach for patients with ISM remain the focus of the ongoing trial. (Funded by Blueprint Medicines Corporation; ClinicalTrials.gov number, NCT03731260.)