Airway changes in patients with sleep apnea using AdvanSync2 Class II correctors – a case series

Background. Obstructive sleep apnea (OSA) is a condition that affects a patient’s ability to sleep normally, predisposing them to many risks and reduced quality of life. Myofunctional therapy has been proven to increase the airway space according to literature. Aim. To report the effects of AdvanSync2 Class II corrector in the management of 3 orthodontic patients who reported sleeping difficulties due to breathing problems and retrognathic mandible. Case presentation. Three patients reported to Department of Orthodontics and Dentofacial Orthopaedics with Class II malocclusion associated with sleep apnea requiring treatment. Clinical examination revealed a retrognathic mandible with airway constriction in all subjects. A non-extraction approach using an AdvanSync2 Class II corrector (Ormco Corp, Glendora, Calif) with fixed appliances was considered. Lateral cephalometric records were obtained at three stages: pre-treatment, post functional and prefinishing/post treatment. The airway was divided into 3 parts in the lateral cephalogram: velopharynx, hypopharynx and glossopharynx. The most constricted part of the airway was noted. Pre and post treatment lateral cephalograms were compared to assess the changes in airway dimensions after using AdvanSync2. Significant enhancement in airway dimensions was noted in all three parts (velopharynx, glossopharynx and hypopharynx) in all patients. Conclusion. Airway assessment is an important aspect in orthodontic diagnosis. Use of the AdvanSync2 Class II corrector in combination with fixed orthodontic appliances enhanced quality of life in Class II patients by improving airway dimensions. This approach can be recommended in the management of mild to moderate Class II malocclusions associated with mandibular retrognathism and airway constriction.

Mucus Release and Airway Constriction by TMEM16A May Worsen Pathology in Inflammatory Lung Disease

Activation of the Ca2+ activated Cl- channel TMEM16A is proposed as a treatment in inflammatory airway disease. It is assumed that activation of TMEM16A will induce electrolyte secretion, and thus reduce airway mucus plugging and improve mucociliary clearance. A benefit of activation of TMEM16A was shown in vitro and in studies in sheep, but others reported an increase in mucus production and airway contraction by activation of TMEM16A. We analyzed expression of TMEM16A in healthy and inflamed human and mouse airways and examined the consequences of activation or inhibition of TMEM16A in asthmatic mice. TMEM16A was found to be upregulated in the lungs of patients with asthma or cystic fibrosis, as well as in the airways of asthmatic mice. Activation or potentiation of TMEM16A by the compounds Eact or brevenal, respectively, induced acute mucus release from airway goblet cells and induced bronchoconstriction in mice in vivo. In contrast, niclosamide, an inhibitor of TMEM16A, blocked mucus production and mucus secretion in vivo and in vitro. Treatment of airway epithelial cells with niclosamide strongly inhibited expression of the essential transcription factor of Th2-dependent inflammation and goblet cell differentiation, SAM pointed domain-containing ETS-like factor (SPDEF). Activation of TMEM16A in people with inflammatory airway diseases is likely to induce mucus secretion along with airway constriction. In contrast, inhibitors of TMEM16A may suppress pulmonary Th2 inflammation, goblet cell metaplasia, mucus production, and bronchoconstriction, partially by inhibiting expression of SPDEF.

Effects of (a Combination of) the Beta2-Adrenoceptor Agonist Indacaterol and the Muscarinic Receptor Antagonist Glycopyrrolate on Intrapulmonary Airway Constriction

Expression of bronchodilatory β2-adrenoceptors and bronchoconstrictive muscarinic M3-receptors alter with airway size. In COPD, (a combination of) β2-agonists and muscarinic M3-antagonists (anticholinergics) are used as bronchodilators. We studied whether differential receptor expression in large and small airways affects the response to β2-agonists and anticholinergics in COPD. Bronchoprotection by indacaterol (β2-agonist) and glycopyrrolate (anticholinergic) against methacholine- and EFS-induced constrictions of large and small airways was measured in guinea pig and human lung slices using video-assisted microscopy. In guinea pig lung slices, glycopyrrolate (1, 3 and 10 nM) concentration-dependently protected against methacholine- and EFS-induced constrictions, with no differences between large and small intrapulmonary airways. Indacaterol (0.01, 0.1, 1 and 10 μM) also provided concentration-dependent protection, which was greater in large airways against methacholine and in small airways against EFS. Indacaterol (10 μM) and glycopyrrolate (10 nM) normalized small airway hyperresponsiveness in COPD lung slices. Synergy of low indacaterol (10 nM) and glycopyrrolate (1 nM) concentrations was greater in LPS-challenged guinea pigs (COPD model) compared to saline-challenged controls. In conclusion, glycopyrrolate similarly protects large and small airways, whereas the protective effect of indacaterol in the small, but not the large, airways depends on the contractile stimulus used. Moreover, findings in a guinea pig model indicate that the synergistic bronchoprotective effect of indacaterol and glycopyrrolate is enhanced in COPD.

Stiffening of the Extracellular Matrix is a Sufficient Condition for Airway Hyperreactivity.

The current therapeutic approach to asthma focuses exclusively on targeting inflammation and reducing airway smooth muscle force to prevent the recurrence of symptoms. However, even when inflammation is brought under control, airways in an asthmatic can still hyper-constrict when exposed to a low dose of agonist. This suggests that there are mechanisms at play that are likely triggered by inflammation and eventually become self-sustaining so that even when airway inflammation is brought back under control, these alternative mechanisms continue to drive airway hyperreactivity in asthmatics. In this study, we hypothesized that stiffening of the airway extracellular matrix is a core pathological change sufficient to support excessive bronchoconstriction even in the absence of inflammation. To test this hypothesis, we increased the stiffness of airway extracellular matrix by photo-crosslinking collagen fibers within the airway wall of freshly dissected bovine rings using riboflavin (vitamin B2) and Ultraviolet-A radiation. In our experiments, collagen crosslinking led to a two-fold increase in the stiffness of the airway extracellular matrix. This change was sufficient to cause airways to constrict to a greater degree, and at a faster rate when they were exposed to 10-5M acetylcholine for 5 minutes. Our results show that stiffening of the extracellular matrix is sufficient to drive excessive airway constriction even in the absence of inflammatory signals.

A case of venlafaxine-induced angioedema in an older adult

Angioedema is a serious adverse event that can manifest as lower extremity edema, face swelling, rash, hives, and a swollen tongue, which can sometimes lead to airway constriction and death. It is a well-documented reaction within the angiotensin-converting enzyme inhibitor drug class, where the bradykinin pathway leads to angioedema. We report a case where a patient experienced angioedema after taking venlafaxine. We evaluated other antidepressants as potential treatment options for the patient. We further examined potential cross-reactivity between antidepressants in order to find alternative medications for patients that experience serious adverse effects.

Dynamic airway constriction in rats: heterogeneity and response to deep inspiration

Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and several computational models have predicted that these regions are due to constriction of smaller airways. However, these imaging approaches are often limited in their ability to capture dynamic changes in small airways, and the patterns of constriction are heterogeneous. To directly investigate regional variations in airway narrowing and the response to deep inspirations (DIs), we utilized tantalum dust and microfocal X-ray imaging of rat lungs to obtain dynamic images of airways in an intact animal model. Airway resistance was simultaneously measured using the flexiVent system. Custom-developed software was used to track changes in airway diameters up to generation 19 (~0.3–3 mm). Changes in diameter during bronchoconstriction were then measured in response to methacholine (MCh) challenge. In contrast with the model predictions, we observed significantly greater percent constriction in larger airways in response to MCh challenge. Although there was a dose-dependent increase in total respiratory resistance with MCh, the percent change in airway diameters was similar for increasing doses. A single DI following MCh caused a significant reduction in resistance but did not cause a significant increase in airway diameters. Multiple DIs did, however, cause significant increases in airway diameters. These measurements allowed us to directly quantify dynamic changes in airways during bronchoconstriction and demonstrated greater constriction in larger airways.

1D network simulations for evaluating regional flow and pressure distributions in healthy and asthmatic human lungs

This study aimed to introduce a one-dimensional (1D) computational fluid dynamics (CFD) model for airway resistance and lung compliance to examine the relationship between airway resistance, pressure, and regional flow distribution. We employed five healthy and five asthmatic subjects who had dynamic computed tomography (CT) scans (4D CT) along with two static scans at total lung capacity and functional residual capacity. Fractional air-volume change ([Formula: see text]) from 4D CT was used for a validation of the 1D CFD model. We extracted the diameter ratio from existing data sets of 61 healthy subjects for computing mean and standard deviation (SD) of airway constriction/dilation in CT-resolved airways. The lobar mean (SD) of airway constriction/dilation was used to determine diameters of CT-unresolved airways. A 1D isothermal energy balance equation was solved, and pressure boundary conditions were imposed at the acinar region ( model A) or at the pleural region ( model B). A static compliance model was only applied for model B to link acinar and pleural regions. The values of 1D CFD-derived [Formula: see text] for model B demonstrated better correlation with 4D CT-derived [Formula: see text] than model A. In both inspiration and expiration, asthmatic subjects with airway constriction show much greater pressure drop than healthy subjects without airway constriction. This increased transpulmonary pressures in the asthmatic subjects, leading to an increased workload (hysteresis). The 1D CFD model was found to be useful in investigating flow structure, lung hysteresis, and pressure distribution for healthy and asthmatic subjects. The derived flow distribution could be used for imposing boundary conditions of 3D CFD. NEW & NOTEWORTHY A one-dimensional (1D) computational fluid dynamics (CFD) model for airway resistance and lung compliance was introduced to examine the relationship between airway resistance, pressure, and regional flow distribution. The 1D CFD model investigated differences of flow structure, lung hysteresis, and pressure distribution for healthy and asthmatic subjects. The derived flow distribution could be used for imposing boundary conditions of three-dimensional CFD.

Analisis Pencegahan dan Penanganan Anafilaksis di Masyarakat

Allergies were hypersensitivity reactions of the body to a substance that should not occur in other people, reactions that occur could be group from reactions to mild to severe. Allergies could occur when the body was exposed to allergens in the form of food, dust, drugs, enzymes, hormones, animal hair to contact with water or metal. Reactions that arisen through several stages such as sensitization phase, reaction phase, and slow allergy phase. In allergic reactions there was activation of mast cells in the mucous layer which causes the release of allergic mediators such as histamine, prostaglandin, and cytokines. This mediator would later cause clinical symptoms such as itching, redness, swelling of the eyes, face or lips, sneezing and runny nose. Anaphylaxis was an excessive allergic reaction when the body was exposed to certain allergens that can cause death in sufferers. In anaphylaxis blood vessel dilation occurs accompanied by increased capillary permeability and airway constriction. Symptoms of anaphylaxis could occur in the form of difficulty breathing, a weak and fast pulse, to a decrease in consciousness. Anaphylaxis could be fatal if not treated properly. Anaphylaxis could be prevent by avoiding allergens which could lead to anaphylaxis. If a person experiences anaphylaxis, immediately contact a medical person to be treated.