SABA/ICS prn combo for asthma: AIRSUPRA (albuterol/budesonide)

As of January 2023, AIRSUPRA (albuterol/budesonide), has been approved in the US for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older.

AIRSUPRA (180mcg albuterol/160mcg budesonide) significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate to severe asthma when used as an as-needed rescue medication in response to symptoms.

Albuterol rescue inhalers available prior to 2023 can alleviate acute symptoms, but do not treat the underlying inflammation in asthma. The approval of AIRSUPRA means that for the first time, adults with asthma in the US have a rescue treatment to manage both their symptoms and the inflammatory nature of their disease.

References:

https://www.astrazeneca-us.com/content/az-us/media/press-releases/2023/airsupra-pt027-approved-in-the-us-for-asthma.html

Allergic diseases and sleep problems in children

Allergic rhinitis was associated with a broad range of sleep problems and to a lesser extent in children with asthma and least in children with eczema.

Allergic rhinitis was associated with:

- sleep routine problems
- morning tiredness
- night arousals
- sleep disordered breathing
- restless sleep

Asthma was associated with:

- sleep routine problems
- sleep disordered breathing
- restless sleep

Eczema was associated with restless sleep.

The association between allergic disease and psychological distress was mediated through sleep problems.

References:

https://www.annallergy.org/article/S1081-1206(22)00409-4/fulltext

Add-on etanercept as a treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs. The disease carries considerable morbidity and mortality.

Immunomodulators for SJS/TEN such as systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice.

Emerging evidence suggested that tumor necrosis factor-α antagonists on SJS/TEN may help.

This restrospective review found that add-in of etanercept at the time of initiating conventional therapy could be a superior option to:

- accelerate disease recovery
- reduce the high dose and total amount of systemic steroids

References:

https://www.annallergy.org/article/S1081-1206(22)00441-0/fulltext

https://www.annallergy.org/article/S1081-1206(22)00579-8/fulltext

Against the hygiene hypothesis as the cause of allergic diseases

The article argues against the hygiene hypothesis for causation of allergic diseases:
https://www.annallergy.org/article/S1081-1206(22)00585-3/fulltext

The authors make the case that the basic changes in hygiene, clean water, complete separation of fecal matter from food production, and helminth eradication were complete before most of the major rises in allergic disease. Thus, all the allergic diseases increase occurred “post-hygiene.”

The look for another cause: There is one major change that has decreased the severity of 2 allergic diseases, that is air conditioning and the closing of houses so that air exchange rates are as low as 0.6 air changes per hour. This means that only minimal quantities of pollen can enter the houses but also that houses become drier and less hospitable to mites. Both hay fever and asthma have become less severe since 2000.

References:

https://www.annallergy.org/article/S1081-1206(22)00585-3/fulltext

https://www.annallergy.org/article/S1081-1206(22)00504-X/fulltext

Prognostic factors for polyp recurrence in chronic sinusitis

Chronic rhinosinusitis with nasal polyps is frequently managed with endoscopic sinus surgery (ESS). Prior studies describe individual clinical variables and eosinophil density measures as prognostic for

Polyp recurrence (PR) was found in 39.4% of patients with CRSwNP s/p endoscopic surgery.

Polyp recurrence (PR) was associated with:

- modified Lund-Mackay (MLM) radiographic score (MLM)
- asthma
- eosinophil cationic protein
- anti–double-stranded DNA IgG
- IL-5

A combined model comprised of eosinophil cationic protein, IL-5, pre-ESS MLM, asthma, and anti–double-stranded DNA IgG could accurately predict polyp recurrence (PR).

More in JACI:
https://www.jacionline.org/article/S0091-6749(22)00343-8/fulltext

Blood endotypic signatures in atopic dermatitis

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. AD can be very challenging to manage.

AD is characterized by:

- dense cutaneous dendritic cell and T-cell infiltrates
- increased inflammatory mediators in affected tissues
- barrier defects secondary to the downregulation of differentiation proteins and lipids

AD is associated with a polarized type 2 immune axis.

However, AD is not a homogenous disease. AD may be categorized into multiple clinical phenotypes depending on the underlying molecular signature (endotype).

Read more in JACI here:
https://www.jacionline.org/article/S0091-6749(22)00834-X/fulltext

https://www.jacionline.org/article/S0091-6749(22)00186-5/fulltext

Eosinophilic gastrointestinal diseases: updated nomenclature

Eosinophilic gastrointestinal (GI) diseases (EGIDs) are characterized by tissue eosinophilia and symptoms of esophageal or GI dysfunction. Eosinophilic esophagitis (EoE) diagnostic criteria are well established.

The prevalence of non-EoE EGIDs is much lower, and there are no consensus guidelines for diagnosis as of year 2022.

Particularly problematic has been variable use of the term eosinophilic gastroenteritis to describe EGIDs involving the stomach, small intestine, large intestine, or groupings of these anatomic sites.

EGID is recommended as the umbrella term for pathologic infiltration of the GI tract with eosinophils:

- EoE - Esophageal involvement alone is termed EoE
- non-EoE EGID - any other location of involvement than esophagus can be termed a non-EoE EGID

Individual involved areas of the GI tract should be named specifically, and an “Eo” abbreviation convention should be used.

Read more in JACI here:
https://www.jacionline.org/article/S0091-6749(22)00709-6/fulltext


Chronic rhinosinusitis: Future treatments review in JACI

Chronic rhinosinusitis (CRS) has a major clinical impact and affects 10% of the US population.

CRS presents with 2 major phenotypes:

- CRS with nasal polyps (CRSwNP)
- CRS without nasal polyps (CRSsNP)

Type 2 endotype (cytokines such as IL-4, IL-5, and IL-13; tissue eosinophilia; and local IgE production) comprises 80% to 90% of patients with CRSwNP and 30% to 50% of patients with CRSsNP in Western countries.

CRSwNP in Asia and CRSsNP have more endotypic heterogeneity, with significant subpopulations that have combinations of type 1 (IFN-γ and IL-12), type 2, and type 3 (IL-17 and IL-22) inflammation.

Read more in JACI here:
https://www.jacionline.org/article/S0091-6749(22)00760-6/fulltext


T2 inflammation biomarkers and cytokines

T2 inflammation is characterized by elevations in:

- absolute peripheral or sputum eosinophil counts
- levels of IgE (total and allergen-specific)
- fractional exhaled nitric oxide (FeNO)

The 3 above serve as biomarkers of T2 inflammation.

T2 inflammation is mediated by key cytokines:

- IL-4
- IL-5
- IL-13
- thymic stromal lymphopoietin
- IL-25
- IL-33

IL-4 and IL-13 utilize Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways.

There are biologic therapies targeting these T2 cytokines, reviewed in the article below:
https://www.jacionline.org/article/S0091-6749(22)00840-5/fulltext

Aquagenic urticaria

Aquagenic urticaria (AquaU) is a rare variant of chronic inducible urticaria. In AquaU wheals occur after skin contact with water.

AquaU can be classified as:

- familial AquaU (FAquaU, 18%)
- acquired AquaU (AAquaU, 82%)

The use of second-generation H1 antihistamines (2ndAH1) was reported most often to achieve marked improvement in AquaU

The use of topical therapies in AquaU has controversial efficiency.

More in JACI-IP:
https://www.jaci-inpractice.org/article/S2213-2198(22)00477-9/fulltext