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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.
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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.
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Síndrome de Activación de Mastocitos , Mastocitos , Humanos , Mastocitos/fisiología , Triptasas , Histamina , Leucotrieno E4RESUMEN
The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease.
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Trastornos Mieloproliferativos , Neoplasias , Humanos , Mesilato de Imatinib/uso terapéutico , Diagnóstico Tardío , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Hibridación Fluorescente in Situ , Benzamidas , Proteínas de Fusión Oncogénica/genética , Trastornos Mieloproliferativos/tratamiento farmacológico , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Hypereosinophilic syndrome (HES) encompasses a group of diseases with blood hypereosinophilia and eosinophil-mediated organ dysfunction. HES-associated skin abnormalities, termed cutaneous HES (cHES) here, may influence diagnosis of HES. We sought to better define clinical and histopathological features of cHES. METHODS: We retrospectively reviewed clinical records and cutaneous histopathology of adult patients with HES evaluated at our institution from 2007 to 2018. RESULTS: Forty-one percent (61/150) patients with HES had cHES. The most common clinical morphologies were urticarial (30%) and eczematous (26%). Skin specimens most often showed a spongiotic pattern (31%) with abundant inflammation (50%) including eosinophils (85%). Two specimens (8%) showed interstitial granulomatous dermatitis, and two specimens showed eosinophilic fasciitis (8%). Vasculitis was not identified in any specimen. Eighty-four percent of patients with cHES had ≥1 other organ system involved: pulmonary 41%, ENT 26%, and nervous 23%. Sixty percent (53/89) of non-cHES patients had at least two organ systems involved. Cardiac or gastrointestinal involvement was more common in non-cHES than cHES (p < 0.05). CONCLUSION: Our review confirms that there are no specific clinical or histopathological cHES patterns, but HES should be considered in patients who have eczematous or urticarial reactions of unknown etiology and persistent peripheral hypereosinophilia.
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Síndrome Hipereosinofílico , Urticaria , Vasculitis , Adulto , Humanos , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/patología , Estudios Retrospectivos , Eosinófilos/patología , Pulmón/patologíaRESUMEN
Our current recommendations for diagnosing and treating primary mast cell (MC) activation syndrome make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless of whether allergen-triggered or other pathways are involved; our current understanding of the biomarkers secreted by activated MCs that best discriminate this disorder from other conditions; and the therapeutic drugs that might selectively affect those mediators or MCs themselves. Finding familial or somatic mutations of genes that cause MCs to be hyperactivatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory, and therapeutic criteria for primary MC activation syndromes described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases without overdiagnosing the disorder in patients who likely have other conditions.
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Mastocitosis/diagnóstico , Mastocitosis/terapia , HumanosRESUMEN
BACKGROUND: Our institution has published serial studies of adults and adolescents with anaphylactic events. The first series was published in 1993 and the last was published in 2006. It was our perception that the nature of anaphylactic episodes had changed over the 2 decades since the last review. OBJECTIVE: To determine whether the etiologies and presentations of anaphylaxis have changed during the past decade in our population. METHODS: Patient charts were identified based on International Classification of Diseases, Ninth Revision codes for anaphylactic shock. Charts identified were analyzed for clinical symptoms reported, comorbidities, etiology, investigative testing, and subsequent treatment. These cases were categorized as definitive, probable, or idiopathic based on history and results from testing, similar to our prior reports. RESULTS: We identified 281 possible cases, of which 218 met criteria for anaphylaxis. Of these cases, median age was 42 years (range 9-78) and 64% were female. In the review of cases, 85 (39%) were determined to have a definitive etiology, 57 were determined to have a probable etiology (26%), and 76 (35%) were idiopathic. Interestingly, of those with a definitive cause, the most common etiology identified was galactose-α-1,3-galactose, accounting for 28 cases (33%). Foods were the second leading cause, accounting for 24 cases (28%). CONCLUSION: In this follow-up report on anaphylaxis etiology from a single center, the most common etiology was galactose-α-1,3-galactose. This differs greatly from prior reports from our center. Interestingly, the percentage of cases attributed to idiopathic anaphylaxis decreased from 59% in our previous report to 35% in the present report, which could largely be explained by the number of galactose-α-1,3-galactose cases.
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Anafilaxia/diagnóstico , Anafilaxia/epidemiología , Anafilaxia/etiología , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tennessee/epidemiología , Adulto JovenRESUMEN
BACKGROUND: A history of penicillin allergy is associated with an increased risk of nosocomial infections because patients are exposed to non-beta lactam antibiotics. Ruling out inaccurate penicillin allergy during hospitalization decreases prescription of beta lactam antibiotics. However, the utilization of penicillin allergy testing and timeliness in relation to initiation of antibiotics is not known. OBJECTIVE: Our aim was to describe the proportion and characteristics of patients who underwent inpatient penicillin allergy testing in a hospital without a guideline or infrastructure for inpatient penicillin allergy testing. METHODS: We performed a retrospective chart review of patients admitted to our institution between January 1, 2008, and December 31, 2015, who underwent penicillin allergy testing. RESULTS: Forty-nine patients were identified; 27 (55.1%) were women. The median age was 61.5 years (interquartile range [IQR], 48.5-71 years). The median Charlson-Comorbidity index score was 4 (IQR, 2-5.5). Of these patients, 42.86% (21) were admitted to the intensive care unit, 79.6% of allergy consults were requested by infectious disease physicians, and 87.8% of patients were receiving non-beta lactam antibiotics at the time of testing. The patients received a median of 5 days of antibiotics before testing (range, 0-16 days; IQR, 3-7 days). Antimicrobial therapy was changed in 78.0% of the patients (32), of whom 68.3% (21/32) was attributable to penicillin allergy testing. CONCLUSION: Inpatient penicillin allergy testing is a critical component of antibiotic stewardship; however, an adequate infrastructure is essential for timely evaluation. Inpatient penicillin allergy evaluation requires a multidisciplinary approach focused on patient selection; risk stratification; and optimization of a timely, safe, and cost-effective approach to optimize patient outcomes.
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Hipersensibilidad a las Drogas/epidemiología , Pacientes Internos , Monitoreo Fisiológico/estadística & datos numéricos , Anciano , Alérgenos/inmunología , Hipersensibilidad a las Drogas/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Penicilinas/inmunología , Pautas de la Práctica en Medicina , Calidad de la Atención de Salud , Estudios Retrospectivos , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The risks of using leukotriene receptor antagonists (LTRA) as part of a strategy for stepping down inhaled corticosteroid (ICS) are not well known. OBJECTIVE: To estimate the risk of asthma exacerbation in individuals with stable asthma who start LTRA when stopping ICS or reducing ICS dose. METHODS: We identified articles from a systematic review of English and non-English articles by using a number of data bases. We included randomized controlled trials with a stable asthma run-in period of 4 weeks or more and a follow-up period of at least 3 months. We included studies of individuals with stable asthma who stopped ICS and substituted LTRA (versus continuing ICS) and who reduced ICS while starting LTRA (versus placebo). RESULTS: The search strategy identified 1132 potential articles, of which 52 were reviewed at the full-text level, and four met criteria for inclusion. The single article that met the inclusion criteria for substitution of LTRA for ICS as a step-down strategy found a statistically increased risk of treatment failure of 30.3% for substituting LTRA compared with 20.2% for continuing ICS. The three articles that met the inclusion criteria for comparing LTRA versus placebo in patients with stable asthma who reduce ICS found a modestly decreased risk ratio that favored LTRA of 0.57 (95% confidence interval, 0.36-0.90; I(2) = 0%) in studies that only included individuals >15 years old. CONCLUSION: Only one study addressed the risk of substitution of LTRA for ICS in stable asthma, which limited any strong conclusions about this step-down strategy.
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Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Sustitución de Medicamentos , Glucocorticoides/administración & dosificación , Antagonistas de Leucotrieno/administración & dosificación , Administración por Inhalación , Antiasmáticos/efectos adversos , Humanos , Antagonistas de Leucotrieno/efectos adversos , Oportunidad Relativa , Resultado del TratamientoRESUMEN
Rural health disparities are well documented and continue to jeopardize the long-term health and wellness for the millions of individuals who live in rural America. The disparities observed between urban and rural residents encompass numerous morbidity and mortality measures for several chronic diseases and have been referred to as the "rural mortality penalty." Although the unmet health needs of rural communities are widely acknowledged, little is known about rural health disparities in allergies, asthma, and immunologic diseases. Furthermore, the intersection between rural health disparities and social determinants of health has not been fully explored. To achieve a more complete understanding of the factors that perpetuate rural health disparities, greater research efforts followed by improved practice and policy are needed that account for the complex social context within rural communities rather than a general comparison between urban and rural environments or focusing on biomedical factors. Moreover, research efforts must prioritize community inclusion throughout rural areas through meaningful engagement of stakeholders in both clinical care and research. In this review, we examine the scope of health disparities in the rural United States and the impact of social determinants of health. We then detail the current state of rural health disparities in the field of allergy, asthma, and immunology. To close, we offer future considerations to address knowledge gaps and unmet needs for both clinical care and research in addressing rural health disparities.
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Asma , Población Rural , Humanos , Estados Unidos/epidemiología , Asma/epidemiología , Asma/terapia , Morbilidad , Inequidades en SaludRESUMEN
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.
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OBJECTIVE: To review the literature regarding the pathophysiology of exercise-induced bronchoconstriction (EIB). DATA SOURCES: The databases of PubMed, Ovid MEDLINE, and Scopus were searched for articles using the subject headings and/or keywords asthma, exercise-induced/etiology, exercise, mechanism, pathogenesis, and bronchoconstriction. STUDY SELECTIONS: Articles were selected based on their relevance to the focus of this review, with emphasis on the specific pathophysiologic mechanisms of EIB. RESULTS: EIB occurs in response to the loss of water from the lower airways that results from heating and humidifying large volumes of air in a short period. The resulting hyperosmolar environment activates various cellular mechanisms to release mediators from mast cells, eosinophils, epithelial cells, and sensory nerves. These mediators, in turn, lead to airway smooth muscle contraction and bronchoconstriction. Airway hyperresponsiveness in elite athletes may develop from a process of airway injury and changes in the contractile properties of airway smooth muscle. CONCLUSION: EIB commonly affects individuals with and without clinically recognized asthma, especially those who participate in competitive athletics. Through years of research, the pathophysiology of EIB is now better understood and involves a complex interaction between several different cell types and mediators. Continued research to improve the knowledge regarding the mechanisms of EIB should aid the identification, diagnosis, and treatment of this common condition.
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Broncoconstricción/fisiología , Ejercicio Físico/fisiología , Atletas , Humanos , Lesión Pulmonar/fisiopatologíaRESUMEN
Biologic agents are a rapidly expanding class of medications, and several options are now available for the management of allergic and immunologic disorders. The risks of biologic therapy need to be understood in order to adequately counsel patients and appropriately monitor for potential adverse events. We sought to provide a comprehensive review of the risks and adverse effects reported for the current FDA-approved biologics used in management of allergic and immunologic disorders, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab and tralokinumab. Our review focuses on the risk of hypersensitivity reactions, pregnancy-specific considerations, risk of infection and risk of malignancy. We also highlight drug-specific adverse events and unique safety issues identified in case reports.
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Several monoclonal antibodies have been approved by the Food and Drug Administration (FDA) to treat allergic disorders, including omalizumab, dupilumab, mepolizumab, reslizumab, benralizumab, tralokinumab and tezepelumab, and their indications continue to expand. Although the risks associated with these agents are overall low, hypersensitivity reactions have been described and are reported more frequently with increased use. We provide a comprehensive review of clinical features, diagnosis and management of hypersensitivity reactions attributed to these agents. We aim to provide useful information for the clinician managing hypersensitivity reactions to these monoclonal antibodies, as well as highlight the need for future research to address specific gaps in knowledge.
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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.
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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.)
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Mastocitosis Sistémica , Humanos , Mastocitosis Sistémica/diagnóstico , Pirazoles/uso terapéutico , Pirroles/uso terapéutico , Triazinas/uso terapéuticoRESUMEN
The indications for biologic therapy are expanding. Patients may benefit from different biologics for separate conditions or one condition with multiple pathogenic mechanisms targeted by different biologics. We sought to determine the frequency and safety of combining biologics targeting IgE, IL-5, IL-5R, and IL-4/IL-13 in patients referred to a large academic health system through retrospective chart review. Between January 1, 2015 and July 31, 2021, 25 patients receiving multiple biologics simultaneously were identified. Combinations included omalizumab + mepolizumab (n = 11), omalizumab + dupilumab (n = 6), omalizumab + benralizumab (n = 4), mepolizumab + dupilumab (n = 3), and omalizumab + dupilumab + mepolizumab (n = 1). Sixteen patients were receiving multiple biologics for the same condition, most commonly asthma (n = 10). Nine patients were treated for separate conditions, with chronic spontaneous urticaria and atopic dermatitis being the most common combination (n = 3). The median duration of combination biologic use was 17.5 months. There were no reports of anaphylaxis, other allergic reaction, immune dysfunction, pneumonia, or development of malignancy. The use of multiple biologics appears to be well tolerated in this case series. Prospective study is needed to better determine the efficacy, safety, and cost-effectiveness of this approach.
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Eosinophilic disorders include a wide array of conditions in which eosinophils play a primary pathophysiologic role. While historically treated with corticosteroids and immunosuppressants, knowledge of eosinophil biology has led to the development of several biologics targeting eosinophils. In this review, we discuss the current US Food and Drug Administration (FDA) approved eosinophil-specific biologics targeting IL-5 (mepolizumab and reslizumab) and IL-5R (benralizumab) along with biologics under investigation targeting siglec-8 (lirentelimab). We discuss efficacy and safety data from trials of these medications in conditions including eosinophilic asthma, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), and eosinophilic gastrointestinal disease (EGID). Additionally, we discuss case reports utilizing these medications in conditions including drug reaction with eosinophilia and systemic symptoms (DRESS), allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic pneumonia, among others. While eosinophilic targeting biologic therapy has been successful in eosinophilic asthma, HES, EGPA, and CRSwNP leading to FDA approval for these conditions, trials treating EoE and EGID have been disappointing to date. Given the increasing number of trials utilizing these biologics, it will be imperative for the allergist-immunologist to stay up to date on the latest treatment options to provide the most optimal care for eosinophilic disorders.
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OBJECTIVE: To estimate the potential risk for a future postmarket black box warning (BBW) of US Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) because of the importance for medical clinicians to understand mAb risks and benefits, including unknown future risks, especially for recently approved mAbs. METHODS: The complete dates of the study were March 16, 2020, through May 12, 2021. We searched the FDALabel database online and reviewed the scientific literature to determine current and previous FDA-approved mAbs as of March 2020. The BBWs and initial FDA-issued safety warnings were identified. The BBWs were categorized as premarket or postmarket. For mAbs with specific postmarket BBWs, previous FDA labels were evaluated to identify the presence or absence of an initial corresponding specific FDA warning. RESULTS: In March 2020, a total of 83 mAbs had FDA approval; 33 had BBWs (27 premarket and 13 postmarket BBWs). Of these 33 mAbs, 55 individual specific BBWs existed (36 premarket and 19 postmarket specific warnings). On average, the specific BBWs occurred in the postmarket period at a rate of 3.4% (19/562) per year. Most (73.7%; 14/19) specific postmarket BBWs were preceded by an FDA warning in a median time of 3.61 (interquartile range, 1.36-5.78) years. Specific postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.9% (5/562) per year. CONCLUSION: Specific postmarket BBWs occurred in FDA-approved mAbs at a rate of 3.4% per year. Specific postmarket BBWs not preceded by a specific FDA product label warning had a rate of 0.9% per year.
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BACKGROUND: Risk factors for the pathogenesis of chronic rhinosinusitis (CRS) remain largely undetermined, which is likely due to the heterogeneity of the disease. White blood cell counts have been largely unexplored as a risk factor for CRS even though different types of white blood cells are involved in the inflammatory process of CRS. OBJECTIVE: To investigate causal associations between different types of white blood cells on risk of CRS utilizing a Mendelian randomization (MR) analysis. METHODS: A two-sample MR analysis was performed using respective GWAS summary statistics for the exposure traits (neutrophil count, eosinophil count, basophil count, lymphocyte count, and monocyte count) and outcome trait (CRS). For the exposure traits, the European Bioinformatics Institute database of complete GWAS summary data was used. For the outcome trait, summary statistics for CRS GWAS were obtained from FinnGen. Primary analysis for MR was performed using inverse-variance weighted two-sample MR. Sensitivity analyses included weighted median, MR-Egger, and MR-PRESSO (raw and outlier-corrected). RESULTS: Eosinophils were associated with CRS (OR = 1.55 [95% CI 1.38, 1.73]; p = 4.3E-14). Eosinophil results were similar across additional MR methods. MR results did not demonstrate significant causal relationships between neutrophils, lymphocytes, monocytes, or basophils with CRS. No significant pleiotropic bias was observed. CONCLUSIONS: In a two-sample MR analysis, a potential causal link between blood eosinophil counts and CRS has been demonstrated. In addition, causal relationships between blood counts among other white blood cell types and CRS were not found. Further studies involving genetic variation in CRS are needed to corroborate genetic causal effects for CRS.
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The COVID-19 pandemic has placed increased demands on the ability to safely perform pulmonary procedures in keeping with Centers for Disease Control and Prevention (CDC), American Thoracic Society (ATS), and the Occupational Safety and Health Administration (OSHA) recommendations. Accordingly, the American Academy of Allergy, Asthma & Immunology (AAAAI) Asthma Diagnosis and Treatment convened this work group to offer guidance. The work group is composed of specialist practitioners from academic and both large and small practices. Individuals with special expertise were assigned sections on spirometry, fractional exhaled nitric oxide, nebulized treatments, and methacholine challenge. The work group met periodically to achieve consensus. This resulting document has recommendations for the allergy/asthma/immunology health care setting based on available evidence including reference documents from the CDC, ATS, and OSHA.