Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). CONCLUSIONS: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Identification of 22 novel BTK gene variants in B cell deficiency with hypogammaglobulinemia.

X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK, associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

Minimally invasive biomarker studies in eosinophilic esophagitis: A systematic review.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus that currently requires repeated endoscopic biopsies for diagnosis and monitoring because no reliable noninvasive markers have been identified. OBJECTIVE: To identify promising minimally invasive EoE biomarkers and remaining gaps in biomarker validation. METHODS: We performed a systematic review of EMBASE, Ovid MEDLINE, PubMed, and Web of Science from inception to June 6, 2017. Studies were included if patients met the 2007 consensus criteria for EoE diagnosis, a minimally invasive biomarker was assessed, and the study included at least 1 control for comparison. RESULTS: The search identified 2094 studies, with 234 reviewed at full-text level, and 49 included in the analysis (20 adult, 19 pediatric, 7 pediatric and adult, and 3 not stated). Most (26 of 49) were published after 2014. Thirty-five studies included healthy controls, 9 analyzed atopic controls, and 29 compared samples from patients with active and inactive EoE. Minimally invasive biomarkers were obtained from peripheral blood (n = 41 studies), sponge or string samples (n = 3), oral or throat swab secretions (n = 2), breath condensate (n = 2), stool (n = 2), and urine (n = 2). The most commonly reported biomarkers were peripheral blood eosinophils (n = 16), blood and string eosinophil granule proteins (n = 14), and eosinophil surface or intracellular markers (n = 12). EoE biomarkers distinguished active EoE from healthy controls in 23 studies, atopic controls in 2 studies, and inactive EoE controls in 20 studies. CONCLUSION: Several promising minimally invasive biomarkers for EoE have emerged; however, few are able to differentiate EoE from other atopic diseases.

Appropriateness of epinephrine use in ED patients with anaphylaxis.

BACKGROUND: Studies have demonstrated low rates of emergency department (ED) epinephrine administration for anaphylaxis patients, suggestive of ED undertreatment of anaphylaxis. Our study assessed the appropriateness of ED epinephrine administration in anaphylaxis management. METHODS: A prospective observational study was conducted involving ED patients presenting with possible allergic reactions. Patients and ED providers completed questionnaires regarding the suspected trigger, signs and symptoms, and prehospital treatment. Two board-certified allergists-immunologists independently reviewed the questionnaires, as well as electronic health records, to determine whether the cases represented anaphylaxis and whether ED epinephrine administration was appropriate. RESULTS: Among 174 patients enrolled in the study, 61 (35%) were confirmed to have anaphylaxis. Overall, 47 anaphylaxis patients (77%) received epinephrine either before ED arrival or in the ED. In the latter situation, 24 anaphylaxis patients (39%) received epinephrine and 37 (61%) did not. Of the patients who received ED epinephrine, the allergists-immunologists determined that its administration was appropriate in all cases (95% confidence interval [CI], 83%-100%). Among the 37 patients who did not receive ED epinephrine, the allergists-immunologists determined that nonadministration of epinephrine was appropriate in 36 patients (97%; 95% CI, 84%-100%). The allergists-immunologists determined that overall, ED management was appropriate for 60 (98%) of 61 patients with anaphylaxis (95% CI, 90%-100%). CONCLUSIONS: Although more than 60% of anaphylaxis patients did not receive epinephrine in the ED, the allergists-immunologists deemed ED management appropriate in 98% of total cases. Previous retrospective studies may underestimate the appropriateness of ED anaphylaxis management, particularly when prehospital epinephrine administration is not reported.

Assessing the risks and benefits of step-down asthma care: a case-based approach.

Guidelines have called for pharmacologic stepped care to improve asthma treatment. Therapeutic options which have been approved provide physicians and their patients alternatives for stepping up asthma treatment to achieve control. However, few studies have been performed to identify and characterize procedures for optimal stepping-down treatment in patients with asthma. The resulting uncertainty as well as a lack of prioritization for asthma reassessment once control has been maintained has led to a lack of well-defined procedures for stepping down asthma treatment. However, recent studies provide guidance regarding the risks of stepping down asthma medications. This review uses case-based examples to demonstrate how health care providers may engage patients in discussions regarding guideline recommendations to promote individualized asthma care.

Stepping down inhaled corticosteroids from scheduled to as needed in stable asthma: Systematic review and meta-analysis.

BACKGROUND: Many patients with asthma are potentially overtreated, which results in unnecessary cost and unnecessary exposure to drugs that may result in adverse events. Step down helps reduce overtreatment, may mitigate these harms, and is advocated by major guidelines. Unfortunately, data that support step down are sparse. OBJECTIVES: This systematic review aimed to examine the effect of stepping down from scheduled inhaled corticosteroids (ICS) to as-needed ICS in patients with stable asthma. METHODS: Several electronic databases were systematically searched in April 2014. Articles were screened independently in duplicate. Studies were required to have at least a 12-week follow-up duration and to have compared stepping down from scheduled ICS to as-needed ICS and maintenance of scheduled ICS. Patients were required to have stable asthma as evidenced by at least 4 weeks without asthma exacerbation before intervention. RESULTS: A total of 3025 abstracts were retrieved initially, 77 of which were retrieved for full-text screening. Of these, only two articles were found to be eligible for inclusion, both were randomized controlled trials. By using random effects meta-analysis, it was determined that, after a follow-up of 6-10 months, the relative risk of exacerbation of stepping down from scheduled to as-needed ICS was 1.32 (95% confidence interval [CI], 0.81-2.16; p = 0.27, I(2) = 0%). Those who did not step down had more symptom-free days (standard mean difference 0.26 [95% CI, 0.02-0.49; p = 0.03; I(2) = 22%]). CONCLUSION: There is currently insufficient evidence to associate stepping down from scheduled to as-needed ICS with a change in exacerbations, although it may lead to fewer symptom-free days.

Stepping down from inhaled corticosteroids with leukotriene inhibitors in asthma: a systematic review and meta-analysis.

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.

The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Current asthma guidelines suggest that patients and their providers consider decreasing or stopping controller medications when asthma is stable. OBJECTIVE: We sought to estimate the risk of asthma exacerbation in patients who stop low-dose inhaled corticosteroids (ICSs) compared with those who continue ICSs in randomized controlled trials. METHODS: We identified relevant trials from a systematic review of English-language and non-English-language articles using MEDLINE, EMBASE, and CENTRAL (inception to January 21, 2012). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included randomized controlled trials with a stable asthma run-in period of 4 weeks or more, an intervention to stop or continue ICSs, and a follow-up period of at least 3 months. We pooled results using a random-effects meta-analysis. RESULTS: The search strategy identified 1798 potential articles, of which 172 were reviewed at the full-text level and 7 met the criteria for inclusion. The relative risk for an asthma exacerbation in patients who stopped ICSs compared with those who continued use was 2.35 (95% CI, 1.88-2.92; P < .001; I(2) = 0%), as determined by using data pooled from trials with a mean follow-up of 27 weeks. The pooled absolute risk difference for an asthma exacerbation was 0.23 (95% CI, 0.16-0.30; P < .001; I(2) = 44%). Patients who discontinued ICSs also had a decreased FEV1 of 130 mL (95% CI, 40-210 mL; P = .003; I(2) = 53%), a decreased mean morning peak expiratory flow of 18 L/min (95% CI, 6-29 L/min; P = .004; I(2) = 82%), and an increased mean standardized asthma symptom score of 0.43 SDs (95% CI, 0.28-0.58 SDs; P < .001; I(2) = 0%). CONCLUSION: Patients with well-controlled asthma who stop regular use of low-dose ICSs have an increased risk of an asthma exacerbation compared with those who continue ICSs.

Antihypertensive medication use is associated with increased organ system involvement and hospitalization in emergency department patients with anaphylaxis.

BACKGROUND: Risk factors for increased anaphylaxis severity are poorly understood. Angiotensin-converting enzyme (ACE) inhibitors have been associated with severe anaphylactic reactions in patients with hymenoptera venom allergy. Studies evaluating the association between beta-blockers and severe anaphylaxis have been conflicting. OBJECTIVE: To evaluate the association between antihypertensive medication use and increased anaphylaxis severity. METHODS: We included emergency department anaphylaxis patients aged 18 years and older. Markers of severe anaphylaxis were defined as (1) syncope, hypotension, or hypoxia; (2) signs and symptoms involving 3 or more organ systems; and (3) hospitalization. Antihypertensive medications evaluated included beta-blockers, ACE inhibitors, calcium channel blockers, angiotensin receptor blockers, and diuretics. Simple and multiple logistic regression analyses were conducted to estimate the association between antihypertensive medication use and markers of increased anaphylaxis severity. RESULTS: Among 302 patients with anaphylaxis, 55 (18%) had syncope, hypoxia, or hypotension, 57 (19%) required hospitalization, and 139 (46%) had 3 or more organ system involvement. After adjusting for age, gender, suspected trigger, and preexisting lung disease, beta-blocker, ACE-inhibitor, diuretic, or antihypertensive medication use in aggregate remained associated with both 3 or more organ system involvement and need for hospital admission. The adjusted associations between antihypertensive medication use in aggregate and 3 or more organ system involvement yielded an odds ratio of 2.8 (95% CI, 1.5-5.2; P=.0008) and with hospitalization an odds ratio of 4.0 (95% CI, 1.9-8.4; P=.0001). CONCLUSIONS: In emergency department anaphylaxis patients, antihypertensive medication use is associated with increased organ system involvement and increased odds of hospital admission, independent of age, gender, suspected trigger, or preexisting lung disease.

Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients.

BACKGROUND: Diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis convened by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN). Validation is needed before these criteria can be widely adapted into clinical practice. OBJECTIVE: Our aim was to retrospectively assess the diagnostic accuracy of the NIAID/FAAN criteria for the diagnosis of anaphylaxis in emergency department (ED) patients. METHODS: A retrospective cohort study of ED patients presenting from April to October 2008 was conducted. Patients given a diagnosis of an allergic reaction or anaphylaxis and a subset of patients with related diagnoses were included. Electronic medical records were reviewed and data were abstracted to determine whether the NIAID/FAAN criteria were met. Records were also independently reviewed in a blinded fashion by 2 experienced attending allergists. Final diagnosis by allergists was considered the reference standard. RESULTS: Of 214 patients, 86 (40.2%) met the NIAID/FAAN criteria for anaphylaxis. Allergists gave 61 (28.5%) patients diagnoses of anaphylaxis, 59 (96.7%) of whom satisfied the NIAID/FAAN criteria. The interrater agreement between allergists was substantial (κ = 0.77). The test characteristics of the NIAID/FAAN criteria were as follows: sensitivity, 96.7% (95% CI, 88.8% to 99.1%); specificity, 82.4% (95% CI, 75.5% to 87.6%); positive predictive value, 68.6% (95% CI, 58.2% to 77.4%); negative predictive value, 98.4% (95% CI, 94.5% to 99.6%); positive likelihood ratio, 5.48; and negative likelihood ratio, 0.04. CONCLUSIONS: These results suggest that the NIAID/FAAN criteria are highly sensitive but less specific and are likely to be useful in the ED for the diagnosis of anaphylaxis.

Clinical Follow-up in Patients With Moderate or Severe Allergic-Like Reactions to Iodinated Contrast Material.

OBJECTIVE: To examine follow-up care in patients with a history of acute allergic-like reaction to iodinated contrast material (ICM), including subsequent imaging management, allergy consultation, and repeat ICM exposure and reactions. METHODS: All patients who had a moderate or severe acute allergic-like reaction to ICM after contrast-enhanced CT (CECT) examination from June 1, 2009, to January 1, 2022, at our institution were included. Chart review was performed to determine (1) whether subsequent imaging was not performed or was altered in these patients, (2) whether the patient underwent a subsequent CECT examination, and (3) whether the patient had an allergist consultation. RESULTS: A total of 251 patients were identified. One-third of patients (90 of 251, 36%) had at least one change to their subsequent imaging management due to their reaction, including performing an unenhanced CT (62 of 251, 25%) or MRI (22 of 251, 8.8%) instead of a CECT or not performing a CECT when otherwise clinically indicated (20 of 251, 8.0%). Patients with a prior severe reaction were more likely to have a change in management than patients with a prior moderate reaction (severe: 22 of 32 [69%] versus moderate: 68 of 219 [31%], P < .0001). Only 17 patients (6.8%) had an allergy consult for their ICM reaction. A total of 90 patients underwent 274 subsequent CECT examinations. Repeat allergic-like reactions were observed in one quarter of patients (24 of 90, 27%) and a tenth of CECT examinations (29 of 274, 11%). DISCUSSION: One-third of patients with a history of a moderate or severe allergic-like reaction to ICM had their subsequent imaging care modified due to their reaction.

Aspirin-Exacerbated Respiratory Disease and the Unified Airway: A Contemporary Review.

Aspirin-exacerbated respiratory disease (AERD) is characterized by abnormal arachidonic acid metabolism leading to chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and upper and/or lower respiratory symptoms after ingestion of cyclooxygenase-1 inhibiting nonsteroidal antiinflammatory drugs. Diagnosis is clinical and may involve an aspirin challenge. Inflammatory biomarkers may be useful for diagnosis and treatment monitoring. Conventional medical management for asthma and CRSwNP is often inadequate. Endoscopic sinus surgery followed by continued medical management with or without aspirin desensitization frequently improves symptoms and objective disease measures. Biological agents targeting eosinophilic inflammation are promising alternatives to conventional management.

Acute Adverse Events After Iodinated Contrast Agent Administration of 359,977 Injections: A Single-Center Retrospective Study.

OBJECTIVE: To assess the effects of patient variables, examination variables, and seasonality on allergic-like and physiologic reactions to iodinated contrast material (ICM). PATIENTS AND METHODS: All ICM-enhanced computed tomography (CT) examinations performed from June 1, 2009, to May 9, 2017, at our institution were included. Reactions were identified and categorized as allergic-like or physiologic and mild, moderate, or severe. The effect of patient and examination variables on reactions was evaluated by logistic regression models. RESULTS: A total of 359,977 CT examinations performed on 176,886 unique patients were included. A total of 1150 allergic-like reactions (0.32%; 19 severe [0.005%]) and 679 physiologic reactions (0.19%; 3 severe [0.0008%]) occurred. On multivariable analysis, iopromide had higher rates of reactions compared with iohexol (allergic-like reactions: odds ratio [OR], 3.07 [95% CI, 2.37 to 3.98], P<.0001; physiologic reactions: OR, 2.60 [1.92 to 3.52], P<.0001). Non-White patients had higher rates of reactions compared with White patients (allergic-like reactions: OR, 1.77 [1.36-2.30], P<.0001; physiologic reactions: OR, 1.76 [1.27-2.42], P=.0006). Patient age, sex, prior ICM reaction, ICM dose, CT location, and CT type were also significantly associated with reactions. No significant seasonality trend was observed (P=.07 and .80). CONCLUSION: Non-White patients and patients administered iopromide had higher rates of acute reactions compared with White patients and patients administered iohexol. Younger patients (<50 years vs 51 to 60 years), female sex, history of ICM allergy or other allergies, ICM dose, and contrast-enhanced CT location and type also correlated with higher acute reaction rates.

Development of a machine learning algorithm based on administrative claims data for identification of ED anaphylaxis patient visits.

Background: Epidemiologic studies of anaphylaxis commonly rely on International Classification of Diseases (ICD) codes to identify anaphylaxis cases, which may lead to suboptimal epidemiologic classification. Objective: We sought to develop and assess the accuracy of a machine learning algorithm using ICD codes and other administrative data compared with ICD code-only algorithms to identify emergency department (ED) anaphylaxis visits. Methods: We conducted a retrospective review of ED visits from January 2013 to September 2017. Potential ED anaphylaxis visits were identified using 3 methods: anaphylaxis ICD diagnostic codes (method 1), ICD symptom-based codes with or without a code indicating an allergic trigger (method 2), and ICD codes indicating a potential allergic reaction only (method 3). A machine learning algorithm was developed from administrative data, and test characteristics were compared with ICD code-only algorithms. Results: A total of 699 of 2191 (31.9%) potential ED anaphylaxis visits were classified as anaphylaxis. The sensitivity and specificity of method 1 were 49.1% and 87.5%, respectively. Method 1 used in combination with method 2 resulted in a sensitivity of 53.9% and a specificity of 68.7%. Method 1 used in combination with method 3 resulted in a sensitivity of 98.4% and a specificity of 15.1%. The sensitivity and specificity of the machine learning algorithm were 87.3% and 79.1%, respectively. Conclusions: ICD coding alone demonstrated poor sensitivity in identifying cases of anaphylaxis, with venom-related anaphylaxis missing 96% of cases. The machine learning algorithm resulted in a better balance of sensitivity and specificity and improves upon previous strategies to identify ED anaphylaxis visits.

Urinary fluticasone propionate-17beta-carboxylic acid to assess asthma therapy adherence.

Although the National Asthma Education and Prevention Program Expert Panel Report 3 recommends referral to specialists to address adherence, guidelines do not provide a tool to determine nonadherence. This study was designed to prospectively evaluate the characteristics of urinary analysis of fluticasone propionate-17beta-carboxylic acid (FP17betaCA) as a test to verify if a specific patient has not taken fluticasone propionate (FP) within 16-24 hours. Urine of asthmatic subjects was prospectively analyzed 16-24 hours after witnessed administration of orally inhaled FP using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis; limit of quantitation was 10.3 pg/mL. Results were compared with those from asthmatic subjects not receiving inhaled FP. Thirty asthmatic subjects receiving inhaled FP (2 oral inhalations of FP at 110 micrograms each or 1 oral inhalation twice daily of fluticasone and salmeterol in fixed combination at 250/50 micrograms for 1 week) were compared with 30 asthmatic subjects not receiving FP. FP17betaCA was detected in the urine of 30 of 30 asthmatic subjects receiving FP (median, interquartile range [IQR; 413.5, 212.8-1230.0] range 12.4-3290.0 pg/mL [corrected for urine creatinine: median, IQR {576.2, 188.1-1306.6} range 6.3-5425.9 ng/g Cr]) and was undetectable in 30 of 30 subjects not receiving inhaled FP. The sensitivity and specificity of LC-MS/MS to detect FP17betaCA in urine were 100% (95% exact binomial confidence interval, 88-100) and 100% (95% exact binomial confidence interval, 88-100), respectively. Analysis of FP17betaCA in urine provides a sensitive method that may be used to verify that a specific patient may not have administered FP within a 16- to 24-hour window before testing.

Risk for Postmarket Black Box Warnings in FDA-Approved Monoclonal Antibodies.

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.