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Medical Journal Review

May 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.

A randomized trial of itraconazole vs prednisolone in acute-stage allergic bronchopulmonary aspergillosis complicating asthma

Agarwal R, Dhooria S, Singh Sehgal I, Aggarwal AN, Garg N et al
Chest 2018; 153(3): 656-664. doi:10.1016/j.chest.2018.01.005

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To resolve whether itraconazole as monotherapy has efficacy in the treatment of acute-stage allergic bronchopulmonary aspergillosis (ABPA) complicating asthma, Agarwal and colleagues performed a single center, randomized, non-blinded study, comparing the use of oral itraconazole vs. prednisolone for four months in a group of 131 subjects (prednisolone group, n =63; itraconazole group, n = 68), fulfilling the criteria of acute ABPA. The primary outcomes were proportion of subjects demonstrating a predefined composite response after 6 weeks, percent decline in IgE after treatment, and number of subjects experiencing exacerbation. The secondary outcomes included the time to first exacerbation, change in lung function, and treatment-related adverse effects. The number of subjects exhibiting a composite response was significantly higher in the prednisolone group compared with the itraconazole group (100% vs 88%; P = .007). The percent decline in IgE after 6 weeks and 3 months and the number of subjects with exacerbations after 1 and 2 years of treatment were similar in the two groups. The time to first exacerbation (mean: 437 vs 442 days) and the improvement in lung function after 6 weeks was also similar between the two groups, but side effects were more common in the glucocorticoid arm (P < .001).

In the end, glucocorticoids were found to be more effective than itraconazole in acute-stage ABPA. On the other hand, itraconazole was still found to be effective in a vast majority of subjects (88%), with fewer side effects, and thus remains an attractive alternative in the initial treatment of ABPA. The authors point out that as approximately 12% of patients did not respond to itraconazole, if it is used in acute-stage ABPA the treatment must be closely monitored.

An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1, the major cat allergen

Bonnet B, Messaoudi K, Jacomet F, Michaud E, Fauquert JL et al
Allergy Asthma & Clinical Immunology 2018; 14:14. doi10/1186/s13223-018-0239-8.eCollection 2018

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Ten cat allergens have thus far been identified, but the major allergen responsible for symptoms is Fel d 1. The review by Bonnet and colleagues focuses on this major allergen, exploring recombinant and molecularly engineered forms of Feld 1, which attempt to modify the immunomodulatory properties of this molecule. It is hoped that in the future one of these molecularly engineered forms of Fel d 1 will allow optimization of specific immunotherapy to cat.

Effects of endogenous sex hormones on lung function and symptom control in adolescents with asthma

DeBoer MD, Phillips BR, Mauger DT, Zein J, Erzurum SC et al
BMC Pulmonary Medicine 2018; 18: 58. doi:10.1186/s12890-018-0612-x

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It is well known that in pre-puberty asthma is more prevalent in males, but after puberty through middle-age, asthma is more prevalent in females. Some believe that it is the surge of sex hormones with puberty that might explain this gender switch. In attempt to better understand the effects of sex hormones on lung function and symptoms with puberty, Tanner stage was assessed in 187 children 6–18 years of age (59% severe) enrolled in the NIH/NHLBI Severe Asthma Research Program, and the effects of circulating sex hormones (n = 68; testosterone, dehydroepiandrosterone sulfate (DHEA-S), estrogen, and progesterone) on lung function and 4 week symptom control (ACQ6) in cross-section were tested by linear regression.

The authors found that pre−/early to late puberty, lung function did not change significantly but ACQ6 scores improved in males with severe asthma. Females however demonstrated lower post-BD FEV1% and FVC% and worse ACQ6 scores with late puberty assessed by breast development. In males log DHEA-S levels, which increased by Tanner stage, associated positively with pre- and post-BD FEV1%, pre-BD FVC %, and negatively (improved) with ACQ6. The authors conclude that these results support beneficial effects of androgens on lung function and symptom control and weak deleterious effects of estradiol on lung function in children with asthma and suggest longitudinal studies to confirm these cross-sectional findings.

Value of a second dose of epinephrine during anaphylaxis: A patient/caregiver survey

Song TT, Brown D, Karjalainen M, Lehnigk U, Lieberman P
Journal of Allergy and Clinical Immunology: In Practice 2018; published online ahead of print, 3 February. doi:10/1016/j.jaip.2018.01.019

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When suffering from an anaphylactic episode, a second epinephrine dose is required in 16% to 36% of patients. For this reason it is important to carry a second dose. To evaluate real-world use of epinephrine auto-injectors (EAIs) the authors performed a survey exploring several domains relevant to anaphylaxis and EAI use from U.S. patients and caregivers who received an EAI prescription in November 2015. The survey was completed by 953 respondents (505 patients and 448 caregivers). They found that 786 (82%) of the respondents did not carry 2 EAIs all the time, with the main reason given that they had 1 EAI in another location with most keeping at least 1 EAI at home (84%). Interestingly during training, most respondents (64%) were instructed to always carry 1 EAI and keep the other in another location. Furthermore, they found that 50% of the respondents reported the use of a second epinephrine dose in a previous event and 45% of the 73 respondents who sought emergency care did so because of the unavailability of a second dose.

Taken together, this study suggests poor adherence in patients and caregivers as well as flaws in patient training regarding anaphylaxis guidelines (which recommends that more than 1 EAI available at all times) can translate to adverse outcomes.

A novel human mast cell activation test for peanut allergy

Santos AF, Couto-Francisco N, Bécares N, Kwok M, Bahnson HT, Lack G
Journal of Allergy and Clinical Immunology 2018; published online ahead of print, 3 May. doi:10.1016/j.jaci2018.03.011

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Peanut allergy (PA) has a significant effect on patients’ and caregivers’ lives; thus, an accurate diagnosis is extremely important. Present diagnostic tests are inaccurate and as a result, a considerable proportion of patients need to undergo an oral food challenge, which is resource intensive and carries the risk of causing allergic reactions, including anaphylaxis. Recent research by this group demonstrated improved accuracy with the use of the basophil activation test (BAT), and in this paper they attempted to further  their work by investigating the ability to elicit peanut-induced cell activation by passive sensitization of LAD2 mast cells with patients’ plasma – the mast cell activation test (MAT). To do so, they studied 174 children undergoing evaluation for PA, including 73 children with PA, 60 peanut sensitization but not allergic (PS) children and 41 nonsensitized/nonallergic (NA) children. Their evaluation included clinical assessment, skin prick tests, blood collection for Immuno-CAP; and OFCs to peanut, as well as an MAT.

They found that the MAT discriminated children with PA from those with PS and overcame the main obstacle of the BAT, as it did not require fresh blood cells from the patient, thus allowing deferred testing. Furthermore, they found the MAT demonstrated very high specificity when used to diagnose PA, concluding that the MAT can be used to diagnose PA in a sequential manner when conventional tests fail and further suggest that it will likely be applicable to other food allergens.

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