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Medical Journal Review

February 2021

WAO Reviews – Editors’ Choice

Articles are selected for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases by Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, WAO Reviews Editor.

Disulfide disruption reverses mucus dysfunction in allergic airway disease
Morgan LE, Jaramillo AM, Shenoy SK, Raclawska D,  Emezienna NA et al
Nature Communications 2021; 12(1):249

Although airway mucus is essential for lung defense, excessive mucus in asthma obstructs airflow, leading to severe and potentially fatal outcomes. Our present asthma armamentarium has minimal effects on mucus, and our lack of therapeutic options stems from a poor understanding of mucus function and dysfunction at a molecular level.

As noted by the authors of this paper, biophysical properties of mucus are controlled by mucin glycoproteins that polymerize covalently via disulfide bonds. Once secreted, mucin glycopolymers can aggregate, form plugs, and block airflow. In this study, Morgan and colleagues demonstrate that reducing mucin disulfide bonds disrupts mucus in human asthmatics and reverses pathological effects of mucus hypersecretion in a mouse allergic asthma model. Specifically, in mice, inhaled mucolytic treatment loosens mucus mesh, enhances mucociliary clearance, and abolishes airway hyperreactivity (AHR) to methacholine. The authors found that the AHR reversal was directly related to reduced mucus plugging. The authors suggest that these findings highlight the need for developing treatments to inhibit effects of mucus hypersecretion in asthma.

Manifesto on United Airways Diseases (UAD): An Interasma (Global Asthma Association – GAA) document
Tiotiu A, Novakova P, Baiardini I, Bikov A, Chong Neto H et al
Journal of Asthma 2021; 25:1-33, Published online ahead of print

The large amount of evidence and renewed interest of the involvement of the upper and lower airways in infectious and inflammatory diseases led Interasma (Global Asthma Association – GAA) to develop a position paper on United Airways Diseases (UAD). This expert paper describes the evidence gathered to date and defines and explores issues regarding UAD (rhinitis, rhinosinusitis, and nasal polyposis), and concomitant/comorbid lower airways disorders (asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, obstructive sleep apnea) with the aim of challenging assumptions, fostering commitment, in an attempt to catalyze change.

The authors note that UAD refers to coexistence of upper and lower airways involvement, driven by a common pathophysiological mechanism, leading to a greater burden on patient’s health status and requiring an integrated diagnostic and therapeutic plan. It has been clearly shown that upper and lower airways diseases influence disease control and ultimately the patient’s quality of life. The authors stress that patients with UAD need to have a timely and adequate diagnosis, treatment, and, when recommended, referral for management in a specialized center. Diagnostic testing including skin prick or serum specific IgE, lung function, fractional exhaled nitric oxide, polysomnography, allergen-specific immunotherapies, biological therapies, and homebased continuous positive airway pressure (CPAP) whenever these are indicated, should be part of the management plan for UAD.

The authors conclude by stressing that education of medical students, physicians, health professionals, patients, and caregivers on the UAD is needed.

Hypersensitivity reactions to multiple anti-tuberculosis drugs
Shin HJ, Chang JS, Kim MS, Koh BG, Park HY et al
PLoS One 2021; 16(2):e0246291

To better understand hypersensitivity reactions to anti-tuberculosis (TB) drugs, Shin and colleagues performed a retrospective analysis comparing the clinical manifestations and treatment outcomes of single vs. multiple drug hypersensitivity reactions (DHRs). They found a total of 28 patients with anti-TB DHRs, as confirmed by drug provocation testing. Seventeen patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2– 73.2). Of the total group, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0–3.0). Rifampin was the most common drug to cause a DHR in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543).

Are volatile organic compounds able to identify airflow decline in asthma?
Graff S, Zanella D, Stefanuto PH et al
Journal of Asthma and Allergy 2021;14:67-70

This study by Graff et al prospectively examined a population of unselected asthmatics performing measure of fraction of exhaled nitric oxide (FeNO), spirometry, sputum induction, and VOC measurements collected at baseline and at the 5-year-follow-up visit. Subjects with asthma were allocated into two groups (airflow decliners and non-decliners) retrospectively, based upon their lung function (post-BD FEV1) decline per year. They found that VOCs were not able to discriminate between airflow decliners and non-decliners. Furthermore, airflow decliners and non-decliners had similar levels of FeNO, blood and sputum eosinophils at baseline.

A challenge for allergologist: Application of allergy diagnostic methods in mast cell disorders
Romantowski J, Górska A, Niedoszytko M, Gulen T, GruchaƂa-Niedoszytko et al
International Journal of Molecular Science 2021; 22(3):1454

In this article, Romantowski and colleagues examine the diagnosis and management of patients with  mastocytosis and concomitant mast cell activation syndromes (MCAS), with special emphasis on novel diagnostic tests and management, including allergen microarrays, recombinant allergen analysis, basophil activation tests, optimal prophylaxis, and specific therapies.

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