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Medical Journal Review

June 2018

WAO Reviews – Editors' Choice

The Editors select articles for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases, and whenever possible they seek articles that everyone can access freely. The Editors’ Choice comes to you from Juan Carlos Ivancevich, MD, WAO Web Managing Editor, and summary author, John J. Oppenheimer, MD, FACAAI, FAAAAI, WAO Reviews Editor.

The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review
Blaiss MS, Hammerby E, Robinson S, Kennedy-Martin T, Buchs S
Annals of Allergy Asthma & Immunology 2018; Published online ahead of print (4 April). DOI:10.1016/j.anai.2018.03.028

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In this article, Blaiss and colleagues evaluate the literature regarding the burden of allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) in adolescents. They identified 27 articles, finding that AR symptoms that rated most bothersome were rhinorrhea, nasal congestion, and itchy eyes. Not surprising was that quality of life (QOL) was worse in adolescents with AR vs controls regardless of QOL instrument used. Interestingly, nasal symptoms and nasal obstruction were more likely to be associated with poor QOL in adolescents than in adults or younger children, respectively. Furthermore, they found that daily functioning and sleep were also negatively affected by AR. In addition, a detrimental effect on absenteeism, school productivity, and academic performance was reported. They conclude that although AR and ARC are often perceived as trivial conditions, this review demonstrates that their effect on adolescent life is negative and far-reaching, reinforcing that clinicians gain a greater understanding of the unique burden of AR and ARC in adolescents to ensure they receive prompt and appropriate care.

Intramuscular versus oral corticosteroids to reduce relapses following discharge from the emergency department for acute asthma
Kirkland SW, Cross E, Campbell S, Villa-Roel C, Rowe BH
Cochrane Database of Systematic Reviews 2018; Published online ahead of print (2 June). DOI:10.1001/14651858.CD012629.pub2


It is well accepted that systemic corticosteroids are a major part in the treatment of moderate to severe acute asthma; however, there is no clear evidence regarding the most effective route of administration for improving outcomes in patients discharged from an acute care facility. The goal of the Cochrane review was to examine the effectiveness and safety of a single dose of intramuscular (IM) corticosteroids provided prior to discharge compared to a short course of oral corticosteroids in the treatment of acute asthma patients discharged from an emergency department (ED) or equivalent acute care setting. To do so, they relied upon their well validated Cochrane Airway Group approach of the literature search, and utilized the GRADE approach to assess the quality of the evidence.

They identified 9 studies involving 804 participants (IM= 402 participants; oral = 402 participants) that met the review inclusion criteria. Four studies enrolled children (n = 245 participants), while five studies enrolled adults (n = 559 participants). All of the pediatric studies compared intramuscular (IM) dexamethasone to oral prednisone/prednisolone. In the adult studies, the IM corticosteroid evaluated included methylprednisolone, betamethasone, dexamethasone, or triamcinolone, while the regimen of oral corticosteroids consisted of prednisone, methylprednisolone, or dexamethasone. Only five studies were placebo controlled. They found that intramuscular and oral corticosteroids were similarly effective in reducing the risk for relapse (RR 0.94, 95%CI 0.72 to 1.24; 9 studies, 804 participants; I² = 0%; low-quality evidence). No subgroup differences in relapse rates were seen between pediatric and adult participants (P = 0.71), relapse occurring within or after 10 days post-discharge (P = 0.22), or participants with mild/moderate or severe exacerbations (P = 0.35). Although no statistical difference between participants receiving IM versus oral corticosteroids were noted regarding the risk for adverse events (RR 0.83, 95% CI 0.64 to 1.07; 5 studies, 404 participants; I² = 0%; moderate-quality evidence), an estimated 50 fewer patients per 1000 receiving IM corticosteroids reported experiencing adverse events (95% from 106 fewer to 21 more), but they did acknowledge inconsistent reporting of specific adverse events across the studies. Furthermore, there were no differences in the frequency of specific adverse events including nausea and vomiting, pain, swelling, redness, insomnia, or personality changes.

In conclusion, the authors found insufficient evidence to identify whether IM corticosteroids are more effective in reducing relapse compared to oral corticosteroids among children or adults discharged from an ED or equivalent acute care setting for acute asthma. They suggest further studies comparing the effectiveness of IM versus oral corticosteroids could provide further evidence clarity. Furthermore, they note that there is a need for further regarding this corticosteroid comparison and also suggest that other factors, such as patient preference and potential issues with adherence, may dictate practitioner prescribing.

Pollen and spore monitoring in the world
Buters JTM, Antunes C, Galveias A, Bergmann KC, Thibaudon M, Galán C, Schmidt-Weber C, Oteros J
Clinical and Translational Allergy 2018; 8:9. DOI:10.1186/s13601-018-0197-8

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Unlike government funded monitoring of non-biological (“chemical”) components in ambient air (such as ozone, Sulphur dioxide, and nitrogen oxides), biological particles, such as pollen and fungal spores, generally rely upon monitoring networks that are not publicly funded and data are not often freely available. The information regarding which biological particle is being monitored, where and by whom, is often not known, even by allergists. The purpose of this study was to review pollen monitoring stations throughout the world and to create an interactive visualization of their distribution, via: (a) a review of the recent and historical bibliography related to pollen and fungal spore monitoring, and (b) personal surveys of the managers of national and regional monitoring networks. Through this, they were able to create an inventory of the active pollen and spore monitoring stations in the world and found that there are at least 879 active pollen monitoring stations in the world, most of which are in Europe (> 500). These stations can be visualized through an interactive and on-line platform and can be adjusted to the users’ needs, with updates provided regularly as new stations become available.

Association of long-term risk of respiratory, allergic, and infectious diseases with removal of adenoids and tonsils in childhood
Byars SG, Stearns SC, Boomsma JJ
JAMA Otolaryngology – Head and Neck Surgery 2018; Published online ahead of print (7 June). DOI:10.1001/jamaoto.2018.0614

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Although removal of adenoids and tonsils to treat obstructed breathing or recurrent middle-ear infections is a common pediatric procedure, little is known about their long-term health consequences. To better understand the potential sequela of this procedure, the authors determined an estimate of long-term disease risks associated with adenoidectomy, tonsillectomy, and adenotonsillectomy in childhood by performing a population-based cohort study of up to 1,189,061 children born in Denmark between 1979 and 1999. Participants in the case and control groups were selected such that their health did not differ significantly prior to surgery. Participants were classified as exposed if adenoids or tonsils were removed within the first 9 years of life. Of the initial group, a total of 17,460 underwent adenoidectomy, 11,830 tonsillectomy, and 31,377 adenotonsillectomy; and 1,157,684 were in the control group. They found that these surgeries were associated with increased long-term risks of respiratory, infectious, and allergic diseases. Although rigorous controls for confounding were used where such data were available, it is possible these effects could not be fully accounted for. The authors conclude that it is important to consider long-term risks when making decisions to perform tonsillectomy or adenoidectomy.

Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma
Gao J, Wu F
Allergy Asthma & Clinical Immunology 2018; 14:21. DOI:10.1186/s13223-018-0248-7

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Although induced sputum is the gold standard test for phenotyping asthma, both the fractional exhaled nitric oxide (FeNO) and blood eosinophils are alternative biomarkers of eosinophilic airway inflammation used in the diagnosis and management of asthma. Unfortunately, the correlation between sputum eosinophils, FeNO and blood eosinophils have varied depending on the specific study. Thus, the goal of this study was to investigate the clinical application of the correlation between sputum eosinophils, FeNO and blood eosinophils with uncontrolled asthmatic patients. It also examined the relationships between these biomarkers in bronchial reversibility and bronchial hyper-responsiveness (BHR), through evaluating 75 uncontrolled asthmatic patients (symptom control and future risk of adverse outcomes).

All patients underwent extensive testing during 1 session, including: FeNO, spirometry, BHR or bronchodilator reversibility, sputum induction and blood collection, with eosinophilic airway inflammation defined as sputum eosinophils≥2.5% or FeNO levels≥32 parts per billion (ppb). A significant positive relationship was seen between the percentage of sputum eosinophils and FeNO (r=0.4556; p<0.0001) and the percentage of blood eosinophils (r=0.3647; p=0.0013), and a significant negative correlation was between percentage of sputum neutrophils and FeNO (r=−0.3653; p=0.0013). No relationship was seen between FeNO and percentage of blood eosinophils (p=0.5801). ROC curve analysis identified FeNO was predictive of sputum eosinophilia [area under the curve (AUC) 0.707, p=0.004] at a cut-off point of 35.5 ppb (sensitivity=67.3%, specificity=73.9%). Percentage of blood eosinophils was also highly predictive with an AUC of 0.73 (p=0.002) at a cut-off point of 1.5%, sensitivity and specificity were 61.5 and 78.3%, respectively. Although the sputum neutrophil percentage was correlated with FeNO, ROC curve of these parameters did not show useful values (AUC=0.297, p=0.003; AUC=0.295, p=0.021).

Overall, this study demonstrates that inflammatory biomarkers, including FeNO level and blood eosinophils, can accurately predict sputum eosinophilia in patients with uncontrolled asthma. It further suggests that peripheral blood eosinophil is a useful tool which is better than FeNO level for monitoring sputum eosinophilia in uncontrolled asthma.