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.

Antibiotic Exposure and the Risk of Food Allergy: Evidence in the US Medicaid Pediatric Population.

BACKGROUND: Food allergy is a significant public health concern in the United States, especially in the pediatric population. It places substantial clinical and economic burdens on the health care system. Exposure to antibiotics in early childhood is thought to increase the risk of subsequent food allergy. OBJECTIVE: To examine the impact of exposure to antibiotics early in life on time to development of food allergy. METHODS: We conducted a population-based matched cohort study using Medicaid data from 28 states. Antibiotic nonusers were matched 1:1 to antibiotic users on date of birth, sex, race, and state. A Cox proportional hazards regression model was used to evaluate the effect of antibiotic exposure on time to development of food allergy. Sensitivity analyses were performed to assess the robustness of study findings. RESULTS: We matched 500,647 antibiotic nonusers to 500,647 antibiotic users in the Medicaid pediatric population. In the adjusted Cox proportional hazards regression analysis, antibiotic exposure was significantly associated with faster development of food allergy (hazard ratio, 1.40; 95% CI, 1.34-1.45). The magnitude and significance of the association between antibiotic exposure and food allergy did not change in the sensitivity analyses. A significant association between antibiotic exposure and faster development of food allergy was found in 17 of 28 states. CONCLUSION: Compared with antibiotic nonusers, children with antibiotic prescription had an increased risk of food allergy.

Comparative Efficacy of Anti IL-4, IL-5 and IL-13 Drugs for Treatment of Eosinophilic Asthma: A Network Meta-analysis.

BACKGROUND: Several new biologics have been studied in patients with eosinophilic asthma with varying degrees of response on clinical outcomes. No head-to-head trial has directly compared the efficacy of these drugs. OBJECTIVE: To synthesize data on the relative efficacy of benralizumab, dupilumab, lebrikizumab, mepolizumab, reslizumab, and tralokinumab using network meta-analysis. DATA SOURCES: We searched PubMed from inception to December 15th, 2017. DATA EXTRACTION AND SYNTHESIS: We used the 'frequentist' methodology with random effect models using primarily 'netmeta' function in R to generate network meta-analysis results. Outcomes assessed included changes in forced expiratory volume-in 1 s (FEV1), asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ). We also separately analyzed the annualized rate ratios for asthma exacerbations for each drug and compared to placebo. For all outcomes assessed, all drugs were superior to placebo except tralokinumab. In terms of magnitude of effect, dupilumab, followed by reslizumab and benralizumab showed the greatest increase in FEV1, 0.16L (95% CIs: 0.08-0.24), 0.13L (0.10-0.17), and 0.12L (0.08-0.17), compared to placebo. While mepolizumab, followed by dupliumab, benralizumab, and reslizumab showed reductions in ACQ scores, in order of magnitude of effect, dupilumab, followed by mepolizumab, benralizumab, and reslizumab showed the greatest increase in AQLQ scores. All drugs decreased asthma exacerbations but the results were only significant for reslizumab and dupilumab. CONCLUSIONS: All drugs except for tralokinumab showed improvements in FEV1, ACQ, and AQLQ. Only reslizumab and dupilumab were associated with statistically significant reductions in asthma exacerbation rates.

Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency.

Ikaros/IKZF1 is an essential transcription factor expressed throughout hematopoiesis. IKZF1 is implicated in lymphocyte and myeloid differentiation and negative regulation of cell proliferation. In humans, somatic mutations in IKZF1 have been linked to the development of B cell acute lymphoblastic leukemia (ALL) in children and adults. Recently, heterozygous germline IKZF1 mutations have been identified in patients with a B cell immune deficiency mimicking common variable immunodeficiency. These mutations demonstrated incomplete penetrance and led to haploinsufficiency. Herein, we report 7 unrelated patients with a novel early-onset combined immunodeficiency associated with de novo germline IKZF1 heterozygous mutations affecting amino acid N159 located in the DNA-binding domain of IKZF1. Different bacterial and viral infections were diagnosed, but Pneumocystis jirovecii pneumonia was reported in all patients. One patient developed a T cell ALL. This immunodeficiency was characterized by innate and adaptive immune defects, including low numbers of B cells, neutrophils, eosinophils, and myeloid dendritic cells, as well as T cell and monocyte dysfunctions. Notably, most T cells exhibited a naive phenotype and were unable to evolve into effector memory cells. Functional studies indicated these mutations act as dominant negative. This defect expands the clinical spectrum of human IKZF1-associated diseases from somatic to germline, from haploinsufficient to dominant negative.

Antibiotic prescription and food allergy in young children.

BACKGROUND: To assess the relationship between any systemic antibiotic prescription within the first year of life and the presence of an ICD-9-CM diagnosis code for food allergy (FA). METHODS: This was a matched case-control study conducted using South Carolina Medicaid administrative data. FA cases born between 2007 and 2009 were matched to controls without FA on birth month/year, sex, race/ethnicity. Conditional logistic regression was used to model the adjusted odds ratio (aOR) of FA diagnosis. All models were adjusted for presence of asthma, wheeze, or atopic dermatitis. RESULTS: A total of 1504 cases and 5995 controls were identified. Receipt of an antibiotic prescription within the initial 12 months of life was associated with FA diagnosis in unadjusted and adjusted models (aOR 1.21; 95 % CI 1.06-1.39). Compared to children with no antibiotic prescriptions, a linear increase in the aOR was seen with increasing antibiotic prescriptions. Children receiving five or more (aOR 1.64; 95 % CI 1.31-2.05) antibiotic prescriptions were significantly associated with FA diagnosis. The strongest association was noted among recipients of cephalosporin and sulfonamide antibiotics in both unadjusted and adjusted models. CONCLUSIONS: Receipt of antibiotic prescription in the first year of life is associated with FA diagnosis code in young children after controlling for common covariates. Multiple antibiotic prescriptions are more strongly associated with increases in the odds of FA diagnosis.

Cardiovascular safety of long acting beta agonist-inhaled corticosteroid combination products in adult patients with asthma: a systematic review.

INTRODUCTION: Long-acting beta agonists and inhaled corticosteroids combination products (LABA-ICS) are widely used in the treatment of asthma. However, there appears to be little data on their cardiovascular safety. The purpose of this study was to conduct a systematic review of the available studies and trials on the cardiovascular safety of LABA-ICS in adults with asthma. METHODS: Two independent reviewers screened citations from PubMed and National Clinical Trials registry to identify studies and trials on the cardiovascular effects of LABA-ICS in patients with asthma. RESULTS: A total of 15 studies (with 17 cohorts on LABA-ICS to compare with a comparator or placebo) with 5,440 total study participants met the inclusion criteria. Two studies on budesonide-formoterol and one on fluticasone-salmeterol reported treatment emergent cardiovascular adverse events, all of which were dysrhythmias. For comparison, the pooled estimate of the Peto odds ratio (0.72; 95 % confidence interval [CI] 0.17-3; p = 0.65) and the summary risk ratio (0.77; 95 % CI 0.26-2.3; p = 0.64) indicated a nonsignificant difference between LABA-ICS and comparator/placebo groups. CONCLUSIONS: Our systematic review found that few studies and trials reported treatment emergent cardiovascular adverse events with LABA-ICS. However, the Peto odds ratio and risk ratio for these outcomes was statistically nonsignificant. This suggests that LABA-ICS products may have a safe cardiovascular profile in asthma patients.

Fatty acids in breast milk associated with asthma-like symptoms and atopy in infancy: a longitudinal study.

OBJECTIVE: The relationship between fatty acids (FAs) in breast milk and the risk of childhood allergies is controversial. We prospectively investigated the relationship between FAs in colostrum and breast milk and asthma-like symptoms (AS) and atopy in infancy. METHODS: Pregnant women were recruited in Columbia and Charleston, South Carolina. Colostrum and mature milk samples were collected. The concentrations of n-3 FAs (eicosapentaenoic acid, α-linolenic acid, docosapentaenoic acid, and docosahexaenoic acid) and n-6 FAs (linoleic acid, arachidonic acid, and eicosadienoic acid) were determined by gas chromatography. AS were ascertained at 6 and 12 months of age and atopy (skin prick test) at 12 months. FAs were dichotomized (high vs. median and low). Generalized estimating equations were used to determine the effect of FAs on repeated AS, compensating for intra-individual correlations and adjusting for confounders. Log-linear regression was used to analyze atopy. RESULTS: FAs were analyzed in 24 colostrum and 78 breast milk samples. High levels of total n-6 (lipid based) FAs in breast milk were associated with an increased risk of AS in infants (risk ratio (RR) = 2.91; 95% confidence interval (CI): 1.37, 6.18), even after controlling for total n-3 FAs (RR = 2.07, 95% CI: 1.12, 3.85). High levels of total n-3 FAs controlling for n-6 FAs decreased the risk of atopy at the age of 12 months. CONCLUSIONS: High levels of total n-6 polyunsaturated fatty acids (PUFAs) in breast milk are associated with an increased risk for AS, whereas high levels of total n-3 PUFAs decreased the risk of atopy. These data suggest that the effects of n-3 and n-6 PUFAs on allergic disorders should be further explored.

Anti-immunoglobulin e in the treatment of refractory atopic dermatitis.

Atopic dermatitis (AD) is a common diagnosis seen in both children and adults, and it is often the first manifestation of atopic disease. Research has shown a strong correlation between serum IgE levels, the severity of atopic dermatitis, and co-existing asthma and/or allergic rhinitis. Omalizumab (Xolair, East Hanover, NJ; Genentech, South San Francisco, CA) is a monoclonal antibody to human IgE and is currently Food and Drug Administration (FDA) approved for the treatment of asthma. We present 3 patients with severe, treatment resistant atopic dermatitis whose cutaneous symptoms significantly improved by treatment with omalizumab.

X-linked lymphoproliferative disease presenting as pancytopenia in a 10-month-old boy.

X-linked lymphoproliferative disease, also known as Duncan's syndrome, is a rare genetic disorder that causes exaggerated immune responses to Epstein-Barr virus (EBV) infection and often leads to death. Patient presentation varies but can include signs and symptoms typical of EBV, pancytopenia, and fulminant hepatitis.

Single-dose azithromycin microsphere formulation: a novel delivery system for antibiotics.

Azithromycin extended release (Zmax, Pfizer Inc) is a novel single-dose administration formulation of azithromycin which won FDA approval in June 2005 and is currently approved for the treatment of community acquired pneumonia and acute bacterial sinusitis. Azitromycin is incorporated into sustained-release microspheres which release the drug slowly through 200 microm pores. Because of this sustained release mechanism, most of the drug is released into the lower gastrointestinal tract, reducing gastrointestinal side-effects, and allowing for a higher dose to be administered. The unique pharmacological properties and extremely long half-life of azithromycin make this drug well suited to single-dose administration but gastrointestinal side effects have previously hampered single-dose therapy.

A case of allergic bronchopulmonary aspergillosis leading to pneumonia with unusual organisms.

We describe the case of a 50-year-old male with a history of asthma and seizure disorder who presented with a 5-month history of dyspnea. The patient had been treated with multiple courses of antibiotics for presumed community-acquired pneumonia before being determined to have allergic bronchopulmonary aspergillosis (ABPA) by serologic and radiographic criteria. Inflammation resulting from this disease had potentiated a postobstructive pneumonia caused by Nocardia asteroides and Stenotrophomonas maltophilia. Therapy with corticosteroids, trimethoprim sulfa, and voriconazole failed to prevent subsequent destruction of the right upper lobe and the patient required surgical intervention. The discussion emphasizes the diagnostic criteria for ABPA including historic, serologic, and radiographic findings; staging, and treatment. Other possible diagnoses, such as invasive pulmonary aspergillosis, chronic necrotizing aspergillosis, and hyper-IgE syndrome are also briefly reviewed.

Soluble CD23 and interleukin-1 receptor antagonist in human asthmatics following antigen challenge.

Two postulated intrinsic anti-inflammatory mechanisms in asthma include the low affinity IgE receptor, or CD23, and interleukin 1 receptor antagonist (IL-1ra). We investigated the role these mediators play in the asthmatic response by measuring local levels in human asthmatics before and after segmental allergen challenge and examined the effect of inhaled corticosteroids on soluble CD23 and IL-1ra levels. Ten subjects underwent bronchoscopy at baseline and 24 hours after antigen challenge. Prior to challenge and every 12 hours afterward subjects received beclomethasone 252 microg or placebo. Fluid was analyzed for sCD23 and IL-1ra using ELISA immunoassays. Eosinophil percentages significantly increased at 24 hours following antigen challenge. sCD23 levels were generally undetectable at baseline and increased significantly following antigen challenge. IL-1ra levels increased 28-fold in the late-phase response. Beclomethasone significantly reduced the late-phase eosinophil percentage at 24 hours compared with placebo but did not attenuate late-phase sCD23 or IL-1ra levels. Our data showed a significant rise in the levels of two mediators thought to play an important role in the attenuation of the asthmatic response. The finding that steroid treatment did not enhance these levels suggests that this may be an independent approach to asthma therapy that should be investigated.

Alternative medical treatment strategies for chronic hyperplastic eosinophilic sinusitis.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is one of the most common chronic illnesses in the United States. Although CRS has been viewed traditionally as an infectious disease, treatment focused on antibiotics and surgery has not infrequently provided disappointing results. RECENT FINDINGS: Recently much of CRS has been shown to be an eosinophilic inflammatory disease and new anti-inflammatory treatments are being studied. SUMMARY: This review discusses medical management for chronic hyperplastic eosinophilic sinusitis, including antifungal treatment, low-dose macrolide treatment, antilipid mediator therapy, and new immune-modifying treatments.

Topical pimecrolimus in the treatment of human allergic contact dermatitis.

BACKGROUND: Contact dermatitis is a common clinical problem, with prevalent sensitizers being cosmetics, metals, medicines, and plants. Plants of the Toxicodendron species cause allergic contact dermatitis (ACD) in 50% to 70% of the population. Pimecrolimus is an ascomycin macrolactam developed for the treatment of inflammatory skin diseases and approved by the US Food and Drug Administration for atopic dermatitis. There are studies supporting the effectiveness of macrolactams when administered before antigen challenge, but there are no studies describing the effectiveness of these drugs in the treatment of established human ACD. OBJECTIVE: To investigate the effect of topical pimecrolimus in the treatment of Toxicodendron-induced ACD once rash is evident. METHODS: Poison ivy tincture was applied to the bilateral anterior forearms of 12 subjects with Finn Chambers (Allerderm Diagnostic Products, Petaluma, CA). After dermatitis was evident, volunteers treated each arm twice daily with either 1% topical pimecrolimus cream or placebo in a blinded fashion. Outcomes measured were a dermatitis grading score and time to rash and itch resolution. RESULTS: The median +/- SEM time for rash resolution was 16.55 +/- 1.59 days in the treatment group and 16.27 +/- 1.82 days in the placebo group (P = 0.601). The median time for itch resolution was 4.73 +/- 1.56 days in the treatment group and 4.91 +/- 1.59 days in the placebo group (P = 0.167). The average dermatitis score was 2.26 +/- 0.17 in the treatment group and 2.32 +/- 0.15 in the placebo group (P = 0.62). CONCLUSIONS: The application of topical pimecrolimus is ineffective in the treatment of ongoing Toxicodendron-induced ACD.