Assessment of Small Airways with Computed Tomography (CT) Leaves More to be Desired

Computed tomography (CT) assessment of air trapping has been considered useful as a measure of small airway disease. Mean lung density (MLD) and the percentage of the lung field occupied by low attenuation area (LAA%) can be evaluated automatically, and their expiratory/inspiratory (E/I) ratios correlate with asthma severity and spirometry parameters. However, mosaic attenuation, another indicator of air trapping, has been assessed visually, and its functional relevance remains controversial.

This retrospective study of 36 nonsmoking patients with stable asthma attempted to correlate mosaic attenuation, which was assessed visually and automatically, and the E/I ratios of MLD and LAA% with clinical and physiological variables, including impulse oscillometry (IOS) indices.

Only the E/I ratios of MLD and LAA% correlated with forced expiratory volume in 1 s/forced vital capacity of spirometry and the IOS indices of resistance from 5 to 20 Hz.

The automatic method for analysis of mosaic attenuation could be useful, but the results themselves may not be reflecting small airway involvement of asthma, unlike the E/I ratios of MLD and LAA%.

References:

Assessment of Small Airways with Computed Tomography: Mosaic Attenuation or Lung Density. Oguma T et al. Respiration. 2015 Apr 30. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/25924974

Real-Time Activation of One Mast Cell - NEJM video



Real-Time Activation of a Mast Cell by Substance P: Photomicroscopy of one human mast cell placed between two cover slips and perfused with the neuropeptide substance P shows degranulation in real time as observed with the use of Nomarski (three-dimensional) optics.

See the related NEJM article, "Mast Cells, Mastocytosis, and Related Disorders" http://www.nejm.org/doi/full/10.1056/NEJMra1409760

Hymenoptera-induced anaphylaxis: absence of urticaria/angioedema indicates severe anaphylaxis and possibly mastocytosis

Severe anaphylaxis in Hymenoptera venom allergy is associated with a number of risk factors including elevation of baseline serum tryptase (BST), older age, concomitant diseases, and concurrent medications, such as beta-blockers.

This single-center study from Germany included 650 patients fulfilling the criteria for venom immunotherapy.
4 risk factors of severe anaphylaxis were identified:

- elevation of baseline serum tryptase (BST)
- absence of urticaria or angioedema during anaphylaxis
- time interval of less than 5 minutes from sting to onset of symptoms
- senior age

Absence of urticaria/angioedema is an indicator of severe anaphylaxis and possibly mastocytosis, requiring determination of baseline serum tryptase (BST).

References:

Over- and underestimated parameters in severe Hymenoptera venom-induced anaphylaxis: Cardiovascular medication and absence of urticaria/angioedema. Stoevesandt J, Hain J, Kerstan A, Trautmann A. J Allergy Clin Immunol. 2012 May 1. [Epub ahead of print]

http://www.ncbi.nlm.nih.gov/pubmed/22554708?dopt=Abstract

How to do skin testing for tetracycline allergy?

What are tetracyclines?

Tetracyclines are antimicrobial agents that have been in use since 1948. The chemical structure consists of four tetra- hydrocarbon rings with a “cycl” derivation.

What type of reactions are caused by tetracyclines?

Although classical hypersensitivity reactions are considered much less common than for beta-lactams and other antibiotics, tetracyclines have been implicated in both IgE- and T cell-dependent reactions such as fixed drug eruption, more severe reactions like DiHS and TEN, and reactions involving specific organs such as liver, lungs, and the central nervous system amongst others.

Tetracylcines can induce phototoxic and photoallergic reactions. These are T cell responses directed to photoadducts which originate in the skin. They usually occur after 5 days of drug administration although they may appear within hours and develop progressively spreading over the skin not exposed to ultraviolet radiation. The most common tetracycline involved in these reactions has been minocycline. Death can occur specially in those patients who develop fulminant hepatitis or respiratory failure.

How to diagnose tetracycline allergy?

General principles recommended for in vivo diagnostic tests can be followed for the diagnosis of hypersensitivity reactions to tetracyclines. These consist of:

- SPT/IDT for immediate reactions
- IDT/patch testing for non immediate reactions

For doxycycline, concentrations of 20 mg/mL can be used for SPT. For IDT with doxycline, the maximum non-irritative concentration recommended is one tenth dilution of this (2 mg/mL).

Concentrations above these can induce false positive reactions.

Concentrations for patch testing of 5% w/v or w/w in petrolatum have been recommended. In the photopatch test the drug is applied on the back using an aluminum chamber and 48 hours later irradiation with a UVA lamp is made with a dose of 10 jls/cm2. Photopatch tests with doxycycline in appropriate dilution are useful to confirm photoallergic reactions to this antibiotic.

How to interpret the skin test?

A negative skin test does not rule out IgE-mediated allergy. If the skin test is negative, the abscene of allergy should be confirmed with a graded dose drug challenge.

A positive skin test with a non-irritating concentration suggests the presence of drug-specific IgE.

References:

Hypersensitivity reactions to non beta-lactam antimicrobial agents, a statement of the WAO special committee on drug allergy. Mario Sánchez-Borges et al. World Allergy Organization Journal 2013, 6:18.
http://www.waojournal.org/content/6/1/18

General Considerations for Skin Test Procedures in the Diagnosis of Drug Hypersensitivity. Brockow K, et al., Allergy 2012 (January); 57(1):45-51.
http://onlinelibrary.wiley.com/doi/10.1046/j.0105-4538.2001.00001.x-i8/full

Unmet needs for assessment of small airways dysfunction in asthma will hopefully be met by the ongoing ATLANTIS study

An estimated 300 million people suffer from asthma worldwide. Asthma inflammation affects the entire bronchial tree. The small airways, i.e. less than 2 mm diameter, can be affected by inflammation and remodelling. However, their contribution to asthma control and exacerbations has been minimally investigated. Small airways function can be assessed with invasive and non-invasive techniques, including physiological and radiographic testing, in addition to direct and indirect assessments of inflammation. These tests are usually only available in specialised chest clinics. Unfortunately, there is no gold standard tool, or an easy-to-apply measure, available in which to assess small airways dysfunction (SAD). Thus, there is an unmet need to identify SAD easily and correctly across all severities of asthma, and to assess its role in the control of the disease.

The ATLANTIS study ((AssessmenT of smalL Airways involvemeNT In aSthma) aims to:

1) Determine the role of small airways abnormalities in the clinical manifestations of asthma.

2) Evaluate which (combination of) clinical methods best assesses the abnormalities of small airways and large airways dysfunction in asthma and best relates to asthma severity, control and future risk of exacerbations, both cross-sectional and longitudinal.

3) Further develop and validate the small airways dysfunction tool (SADT).

The ATLANTIS study started in 2014 and the first results are expected in 2016. The data gathered could improve our understanding of small airways pathobiology in asthma and provide a database and sample repository to answer future questions.

References: Unmet needs for the assessment of small airways dysfunction in asthma: introduction to the ATLANTIS study. Postma DS et al. Eur Respir J. 2015 Jun;45(6):1534-8. doi: 10.1183/09031936.00214314.
http://erj.ersjournals.com/content/45/6/1534.long
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