RESUMO
Timely diagnosis of systemic mastocytosis (SM) remains challenging due to care heterogeneity. We implemented a standardized approach for SM screening and diagnosis utilizing a novel healthcare system-wide international screening registry. A retrospective analysis assessed rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses before and two years after care standardization. Accuracy of individual and combined SM screening tests - basal serum tryptase (BST) ≥11.5 and ≥20.0 ng/mL, REMA ≥2, monomorphic maculopapular CM, and elevated BST based upon tryptase genotype - was analyzed. Tryptase genotyping and high-sensitivity KIT p.D816V testing increased substantially two years following care standardization. SM diagnoses doubled from 47 to 94 and KIT p.D816V molecular diagnoses increased from 24 to 79. Mean BST and KIT p.D816V variant allele frequency (VAF) values were significantly lower in patients diagnosed after standardization. Hereditary-alpha tryptasemia prevalence was increased in SM prior to care standardization at 4/30 (13.3%) but reflected the general population prevalence two years later at 5/76 (6.6%). Elevated BST based upon genotype and BST ≥11.5 ng/mL had the highest sensitivities at 84.2% and 88.3%, respectively. Presence of monomorphic MPCM, elevated BST based upon tryptase genotype, and the combination of REMA ≥2 with elevated BST based upon tryptase genotype had specificities >90%. BST >20.0 ng/mL had low sensitivity and specificity and was not required to establish any indolent SM diagnosis. Care standardization increased SM diagnosis rates, particularly in patients with low BSTs. Stratifying BST based upon genotype had the best overall sensitivity and specificity of any indolent SM screening test and improved the REMA score specificity.
RESUMO
BACKGROUND Asthma is a common disease in the U.S. POPULATION: Initial therapy in the stepwise approach for asthma management is short-acting ß2-agonist (SABA) therapy as needed for symptom control. However, a significant adverse event that can occur with administration is bronchospasm. Here, we report a case of paradoxical bronchospasm with administration of SABAs during multiple pulmonary function tests (PFTs). CASE REPORT A 25-year-old, non-smoking, African American male with a history of moderate asthma and allergic rhinitis treated with fluticasone/salmeterol diskus, albuterol hydrofluoroalkane (HFA) inhaler, and montelukast presented to our clinic complaining of recurrent episodes of acute shortness of breath immediately following each administration of albuterol for 4 weeks. PFTs were performed with levalbuterol (Xopenex) and albuterol (ProAir), yielding significant decrease in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Nebulized albuterol and ipratropium bromide also improved FEV1 and FVC. He was successfully transitioned to an ipratropium rescue inhaler for asthma exacerbations. CONCLUSIONS Paradoxical bronchoconstriction is the unexpected constriction of smooth muscle walls of the bronchi that occurs in the setting of an expected bronchodilatory response. This phenomenon has been observed with ß2-agonist-containing inhaler formulations and is an under-recognized adverse event. Theories suggest that the formulation excipients can trigger airway hyperresponsiveness in patients with allergically inflamed airways. Removal of excipients or use of anticholinergic inhalers improved respiratory function. Clinicians should be aware of paradoxical bronchospasm as an adverse effect with common inhaler formulations containing ß2-agonists and counsel patients accordingly in the appropriate clinical setting.
