Airway Challenge Research Articles

Airway Microbiota-Host Interactions Regulate Secreted Leukocyte Proteinase Inhibitor Levels and Influence Allergic Airway Inflammation

Abstract Mucosal immune responses fine-tuned by naturally evolved interactions with native microbes influence airway inflammation but are not routinely integrated into experimental models. Here, we leverage a recently discovered murine-adapted airway microbe, Bordetella pseudohinzii (Bph), to investigate how chronic colonization impacts mucosal immunity and the development of allergic airway inflammation (AAI). Despite the persistent colonization, we did not observe significant weight loss in Bph colonized mice. Microscopic examination of the lungs demonstrated the formation of lymphoid aggregates, consistent with inducible Bronchus Associated Lymphoid Tissue (iBALT). Airway colonization of mice with Bph elicits an antigen-specific Th17 immune response that aids in controlling bacterial abundance. Remarkably, when animals undergo allergic airway challenge, mice previously colonized with Bph demonstrate protection from AAI. This phenotype corresponded to a reduction in type 2 cytokines, eosinophilic infiltration, goblet cell metaplasia, and airway hyper responsiveness. Colonization with Bph does not appear to impact the degree of allergic sensitization nor the presentation of allergen in the lung. Further, colonization and the Th17 response was associated with increased expression of Secreted Leukocyte Proteinase Inhibitor (SLPI), an antimicrobial peptide with anti-inflammatory properties. We confirmed these findings in humans by showing that higher levels of SLPI correlate both to improved asthma control and the presence of the asthma-associated bacterium, Haemophilus influenzae. We propose that SLPI could be used as a biomarker of beneficial host-commensal relationships in the airway.

Cetirizine inhibits gender-specific blood cell dynamics upon allergen contact in allergic rhinitis

IgE-mediated inflammatory responses upon allergen contact in allergic rhinitis (AR) are associated with rapid alterations of circulating blood cell numbers detectable in a complete blood count (CBC). Aim of this study was to evaluate whether intake of antihistamines may modulate allergen-induced CBC dynamics in male and female patients.A total of N = 112 specific allergen challenges were performed in otherwise healthy AR subjects. Seventy-two (n = 72) subjects received placebo and forty (n = 40) received cetirizine (H1-receptor antagonist) per os prior to allergen exposure in a randomized, double-blind trial at the Vienna Challenge Chamber (VCC); a subgroup of twenty-five (n = 25) subjects received cetirizine and placebo on different study days (parallel group). Blood samples and symptom scores were taken at baseline and immediately after 6 h of airway challenge simulating ambient allergen contact.Female sex was associated with a pronounced circulating monocyte increase (p < .01) and male sex with an eosinophil decrease (p < .05) in the placebo group, but not in cetirizine treated subjects. The significant increase in segmented neutrophils (p < .001) and decrease in circulating erythrocytes (p < .01) upon allergen challenge was less prominent after cetirizine intake in both sexes. A more prominent thrombocyte increase in female subjects (p < .05) was noted upon allergen exposure, regardless of prior cetirizine intake.Cetirizine inhibited the mobilization of neutrophils, lymphocytes and decline in erythrocyte numbers, but did not affect thrombocyte increase upon allergen challenge. It further diminished gender-specific blood cell dynamics. Overall, as reflected in a simple CBC, cetirizine critically diminished immediate and late innate immune responses subsequent to allergen exposure.

IL-33 induced airways inflammation is partially dependent on IL-9

Asthma is an inflammatory disease of the airways and numerous cytokines contribute to this pathogenesis. It is shown that challenge of airways with IL-33 induces asthma-like pathological changes in mice, but the possible downstream cytokines in this process remain to be characterised. To explore this, we compared changes in the airways of wildtype (WT) and IL-9 deficient mice challenged with IL-33. In line with previous report, per-nasal challenge of WT mice with IL-33 significantly increased the responsiveness of the airways along with infiltration of inflammatory cells, goblet cell hyperplasia, collagen deposition and smooth muscle hypertrophy, and the expression of cytokines compared with control group. Surprisingly, all of these pathological changes were significantly attenuated in IL-9 deficient mice following identical IL-33 challenge. These data suggest that IL-9 is one downstream cytokine relevant to the effects of IL-33 in asthmatic airways and consequently a potential therapeutic target for the treatment of asthma.

Airway challenges in Noma patients undergoing facial reconstructive surgery in Ethiopia

Airway challenges in Noma patients undergoing facial reconstructive surgery in Ethiopia

Mannitol vs. methacholine in the evaluation of airway responsiveness in bakers' asthma.

Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms. Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed. Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol. The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9.

Owner Compliance to an Environmental Management Protocol for Severe Equine Asthma Syndrome

Severe equine asthma (SEA) syndrome is a chronic recurrent respiratory disease, common among adult horses. The disease occurs in genetically susceptible individuals after their exposure to organic dust. Thus, environmental management has proved essential in controlling airway challenge and disease exacerbation. This is a demanding process that can only be achieved through the horse owners’ cooperation. One year after initial diagnosis of SEA in a group of 39 horses, owner compliance to an environmental management protocol was evaluated. The overall compliance to the protocol was poor and the horses’ clinical health and need for pharmacological management was related to the successful implementation of the environmental recommendations provided on disease diagnosis.

Anaesthetic management following tracheal reconstruction: Two heads are better than one as we navigate the airway challenge!

Anaesthetic management following tracheal reconstruction: Two heads are better than one as we navigate the airway challenge!

Neonatal Pierre Robin sequence: An airway challenge addressed with retrograde intubation

We report the case of a 25-day-old neonate posted for glossopexy. The child born at 35 weeks of gestation was diagnosed to have Pierre Robin sequence. The neonate was underweight (2.2 kg), had difficulty in feeding and had respiratory distress needing respiratory assistance and prone position to maintain saturation. Anticipating difficulty in intubation with respect to physiology, age and mismatch of equipment size, we planned retrograde intubation through a laryngeal mask airway with a 2.5 mm ID tube using a needle cricotracheotomy and a flexible-tipped paediatric urological guidewire. Based on our experience, we propose that neonatal difficult airway can be managed using the retrograde intubation technique.

Use of the GlideScope® for enhanced airway challenges in Treacher Collins syndrome.

Use of the GlideScope® for enhanced airway challenges in Treacher Collins syndrome.

Airway Management in the Prehospital, Combat Environment: Analysis of After-Action Reviews and Lessons Learned.

Airway compromise is the second leading cause of potentially survivable death on the battlefield. Studies show that airway management is a challenge in prehospital combat care with high error and missed opportunity rates. Lacking is user information on the perceived reasons for the challenges. The US military uses several performance improvement and field feedback systems to solicit feedback regarding deployed experiences. We seek to review feedback and after-action reviews (AARs) from end-users with specific regard to airway challenges noted. We queried the Center for Army Lessons Learned (CALL), the Army Medical Department Lessons Learned (AMEDDLL), and the Joint Lessons Learned Information System (JLLIS).Our queries comprised a series of search terms with a focus on airway management. Three military emergency medicine expert reviewers performed the primary analysis for lessons learned specific to deployment and predeployment training lessons learned. Upon narrowing the scope of entries to those relevant to deployment and predeployment training, a panel of eight experts performed reviews. The varied nature of the sources lent itself to an unstructured qualitative approach with results tabulated into thematic categories. Our initial search yielded 611 nonduplicate entries. The primary reviewers then analyzed these entries to determine relevance to the project-this resulted in 70 deployment- based lessons learned and four training-based lessons learned. The panel of eight experts then reviewed the 74 lessons learned. We categorized 37 AARs as equipment challenges/malfunctions, 28 as training/education challenges, and 9 as other. Several lessons learned specifically stated that units failed to prioritize medic training; multiple comments suggested that units should consider sending their medics to civilian training centers. Other comments highlighted equipment shortages and equipment malfunctions specific to certain mission types (e.g., pediatric casualties, extreme weather). In this review of military lessons learned systems, most of the feedback referenced equipment malfunctions and gaps in initial and maintenance training.This review of AARs provides guidance for targeted research efforts based the needs of the end-users.

Hardware Causing Hard Times: Use of the SuperNO2 VA™ Nasal PAP Device to Address Airway Challenges Caused by Eroding Mandibular Hardware

Hardware Causing Hard Times: Use of the SuperNO2 VA™ Nasal PAP Device to Address Airway Challenges Caused by Eroding Mandibular Hardware

Management of Palatal Fracture and Airway Challenge in A Child — A Red Flag

Airway managements in maxillofacial fracture patients are complex and crucial. Trauma to the maxillofacial region may cause hemorrhage, swelling which may lead to pulmonary aspiration and airway obstruction. Airway managements in maxillofacial fracture patients are complex and crucial. Besides being uncooperative, presence of fractures and soft tissue injuries posed challenges in managing pediatric patient who already have smaller airway opening. This condition is an important red flag which required extra caution from the treating clinicians. A 6-year-old boy was involved in a road traffic accident and presented with profuse bleeding from the oral cavity and nostrils. Physical examination showed oozing of blood with step deformity of the midpalate. Multiple attempts in intubation resulted in failure before succeeding with the aid of suction devices. After intubation was done, intraoral bleeding was successfully managed with transpalatal wiring and nasal packing. The patient was ventilated in the intensive care unit and was extubated two days later. He was discharged well from hospital after one week of admission. Airway management is a rush against time, particularly in a pediatric patient suffering from a palatal fracture. The need for helping hands for suction and child control must be emphasized to ensure the patient’s survival.

Correlation of Bedside Airway Screening Tests With Airway Obstruction During Drug-Induced Sleep Endoscopy

Obstructive sleep apnoea hypopnoea syndrome associated with obesity poses major perioperative airway challenge. Drug-induced sleep endoscopy (DISE), is a real-time upper airway flexible fiberoptic nasoendoscopy in awake and sedation/anaesthesia-induced sleep. The aim of current study was to assess the correlation of bedside airway screening tests with level of obstruction during DISE. Study was performed in endoscopy suite. Parameters calculated in 40 study group patients were Berlin questionnaire responses, Apnea hypopnea index (AHI), interincisor distance, Mallampati classification (MPC), neck circumference (NC), thyromental distance (TMD), NC/TMD ratio, sternomental distance (SMD), upper lip bite test, lateral cephalometry derived gonial angle and mentohyoid distance (MHD), Muller’s manoeuvre during awake nasoendoscopy, Croft–Pringle grade of airway obstruction during DISE and effect of jaw thrust. All patients were American Society of Anesthesiologists physical status 1 and 2 with AHI > 30. Positive responses to Berlin questionnaire, body mass index and AHI increased with increasing grade of DISE. DISE grades 1–5 were observed in 0% (0), 5% (2), 37.5% (15), 27.5% (11) and 30% (12) patients respectively. Muller’s manoeuvre showed lateral wall collapse in 40% (16) patients and concentric collapse in 40% (16) patients. Airway patency improved with jaw thrust in 60% (24) patients. Significant association of DISE was found with MPC (p = 0.028), TMD (p = 0.003), MHD (p = 0.008) and NC/TMD ratio (p = 0.002), effect of Muller’s manoeuvre (p =0.002), and effect of jaw thrust (p = 0.000). Bedside screening tests MPC, TMD, NC/TMD ratio and MHD correlate significantly with level of obstruction during DISE.

Cyclic GMP-AMP Triggers Asthma in an IL-33-Dependent Manner That Is Blocked by Amlexanox, a TBK1 Inhibitor.

Extracellular host-derived DNA, as one of damage associated molecular patterns (DAMPs), is associated with allergic type 2 immune responses. Immune recognition of such DNA generates the second messenger cyclic GMP-AMP (cGAMP) and induces type-2 immune responses; however, its role in allergic diseases, such as asthma, has not been fully elucidated. This study aimed to determine whether cGAMP could induce asthma when used as an adjuvant. We intranasally sensitized mice with cGAMP together with house dust mite antigen (HDM), followed by airway challenge with HDM. We then assessed the levels of eosinophils in the broncho-alveolar lavage fluid (BALF) and serum HDM-specific antibodies. cGAMP promoted HDM specific allergic asthma, characterized by significantly increased HDM specific IgG1 and total IgE in the serum and infiltration of eosinophils in the BALF. cGAMP stimulated lung fibroblast cells to produce IL-33 in vitro, and mice deficient for IL-33 or IL-33 receptor (ST2) failed to develop asthma enhancement by cGAMP. Not only Il-33−/− mice, but also Sting−/−, Tbk1−/−, and Irf3−/−Irf7−/− mice which lack the cGAMP-mediated innate immune activation failed to increase eosinophils in the BALF than that from wild type mice. Consistently, intranasal and oral administration of amlexanox, a TBK1 inhibitor, decreased cGAMP-induced lung allergic inflammation. Thus, cGAMP functions as a type 2 adjuvant in the lung and can promote allergic asthma in manners that dependent on the intracellular STING/TBK1/IRF3/7 signaling pathway and the resultant intercellular signaling pathway via IL-33 and ST2 might be a novel therapeutic target for allergic asthma.

The Anesthetic Management of an Adolescent with Autism Spectrum Disorder and Super-Super Obesity: a Case Report

We report the anesthetic management of a 15-year-old patient with super-super obesity (SSO) and autism spectrum disorder (ASD) presenting for dental surgery and debridement of ingrown toe nails. We discuss the major perioperative implications of SSO and ASD with special attention to the challenges of the morbid obesity difficult airway (MODA). We describe a pragmatic approach for managing MODA—predict difficulty, plan and prepare appropriate equipment, position and preoxygenate the patient, making appropriate pharmacological choices, and continue attention to airway and respiration in the postoperative period. The perioperative implications of a complex combination of ASD with SSO require a multidisciplinary approach with adequate experience, expertise, and equipment.

Short-term high-fat diet feeding protects from the development of experimental allergic asthma in mice.

A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short-term high-fat diet (HFD) feeding on the development of allergic asthma. To delineate the impact of short-term HFD feeding on the development of experimental allergic asthma. Female C57BL/6JRJ mice were fed with a short-term HFD or chow diet (CD) for 12weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)-mediated activation of T cells. Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD-fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD-fed mice. Mucus production was similar in both treatment groups. OVA-induced increases in DC and CD4+ T-cell recruitment to the lungs were significantly attenuated in HFD-fed mice. MHC-II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD-fed compared to CD-fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. These findings suggest that short-term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC-II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short-term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

Maternal allergic asthma during pregnancy alters fetal lung and immune development in sheep: potential mechanisms for programming asthma and allergy.

Experimental maternal allergic asthma in sheep provides an experimental model in which to test impacts on progeny. Fetuses from allergic asthmatic ewes had fewer surfactant-producing cells in lungs. A greater proportion of lymphocytes from thymus were CD44 positive in fetuses from allergic asthmatic ewes than in controls. These changes to fetal development might contribute to poor neonatal lung function and increased risk of allergy seen in offspring of pregnancies complicated by asthma. Asthma is prevalent in pregnancy and increases the risk of disease in offspring, including neonatal respiratory distress and childhood asthma and allergy, but the mechanisms are not understood. We hypothesized that fetal lung structure and immune phenotype in late gestation fetal sheep would be impaired in our sheep model of maternal allergic asthma during pregnancy. Singleton-bearing ewes were either sensitized before pregnancy to house dust mite (HDM, allergic, n=7) or were non-allergic (control, n=5). The ewes were subsequently subjected to repeated airway challenges with HDM (allergic group) or saline (control group) throughout gestation. Tissues were collected at 140±1days gestational age (term, ∼147days). The density of type II alveolar epithelial cells (surfactant protein C-immunostained) in the lungs was 30% lower in fetuses from allergic ewes than in controls (P<0.001), but tissue-to-air space ratio and numbers of leucocytes and macrophages were not different between groups. The proportion of CD44+ lymphocytes in the fetal thymus was 3.5-fold higher in fetuses from allergic ewes than in control ewes (P=0.043). Fewer surfactant-producing type II alveolar epithelial cells may contribute to the increased risk of neonatal respiratory distress in infants of asthmatic mothers, suggesting that interventions to promote lung maturation could improve their neonatal outcomes. If the elevated lymphocyte expression of CD44 persists postnatally, this would confer greater susceptibility to allergic diseases in progeny of asthmatic mothers, consistent with observations in humans. Further experiments are needed to evaluate postnatal phenotypes of progeny and investigate potential interventions.

Hydrogen gas inhalation enhances alveolar macrophage phagocytosis in an ovalbumin-induced asthma model

BackgroundMaintaining an airway clear of bacteria, foreign particles and apoptotic cells by alveolar macrophages is very essential for lung homeostasis. In asthma, the phagocytic capacity of alveolar macrophages is significantly reduced, which is thought to be associated with increased oxidative stress. Hydrogen (H2) has been shown to exert potent antioxidant and anti-inflammatory effects, yet its effects on phagocytosis of alveolar macrophages are unknown. This study is aimed to evaluate the beneficial effects of hydrogen gas inhalation on alveolar macrophage phagocytosis in an ovalbumin (OVA)-induced murine asthma model. MethodsFemale C57BL/6 mice were intraperitoneally sensitized with OVA before they were subject to airway challenge with aerosolized OVA. Hydrogen gas was delivered to the mice through inhalation twice a day (2 h once) for 7 consecutive days. Phagocytic function of alveolar macrophages isolated from bronchoalveolar lavage fluid was assessed by fluorescence-labeled Escherichia coli as well as flow cytometry. ResultsAlveolar macrophages isolated from OVA-induced asthmatic mice showed decreased phagocytic capacity to Escherichia coli when compared with those of control mice. Defective phagocytosis in asthmatic mice was reversed by hydrogen gas inhalation. Hydrogen gas inhalation significantly alleviated OVA-induced airway hyperresponsiveness, inflammation and goblet cell hyperplasia, diminished TH2 response and decreased IL-4 as well as IgE levels, reduced malondialdehyde (MDA) production and increased superoxide dismutase (SOD) activity. Concomitantly, hydrogen gas inhalation inhibited NF-κB activation and markedly activated Nrf2 pathway in OVA-induced asthmatic mice. ConclusionsOur findings demonstrated that hydrogen gas inhalation enhanced alveolar macrophage phagocytosis in OVA-induced asthmatic mice, which may be associated with the antioxidant effects of hydrogen gas and the activation of the Nrf2 pathway.

Adulthood presentation of the neglected childhood temporomandibular joint ankylosis – “An airway challenge”

Temporomandibular joint (TMJ) ankylosis is commonly seen in childhood and its etiology is multifactorial. Common causes include congenital malformations, use of forceps during delivery, local or systemic infections or systemic autoimmune diseases (rheumatoid arthritis, psoriasis, and sickle cell anemia), burns, and trauma. TMJ ankylosis leads to dentofacial deformity, restricted mouth opening, malocclusion, difficulty in mastication, malnutrition, dental caries, poor oral hygiene, impaired speech, and cosmetic disability. Neglected childhood bilateral TMJ patients present in adulthood with micrognathia, retrognathia, and severe symptoms of obstructive sleep apnea (OSA). They have narrow airway passages due to pseudoglossia, subatmospheric intrapharyngeal pressure, and hypotonicity of the oropharyngeal muscles which make the mask ventilation difficult. Highlights of the management of the case include the use of the awake fiber-optic-assisted intubation, a gold standard for difficult airway management, and incorporation of Brainlab Kick navigation station 18070 (USA) aiding in the precise surgical dissection and preventing injuries to great vessels and nerves. Extubation strategy with preextubation dose of hydrocortisone and dexmedetomidine helped in the smooth recovery. Early recovery and rehabilitation were further facilitated with the use of nasal continuous positive airway pressure postextubation which helped in reducing symptoms of OSA and airway obstruction.

Difficult airway challenge in a pediatric patient with Goldenhar syndrome and atrial septal defect for bone anchored hearing aid surgery

Goldenhar syndrome is ocular-auriculo-vertebral dysplasia with cardiac, renal, visceral, and facial abnormalities. Presence of craniofacial and vertebral anomalies increases the risk of difficult airway. Here, we present a case report of a child with Goldenhar syndrome and atrial septal defect (ASD) posted for bone anchored hearing aid surgery. The case report highlights a successful awake retrograde intubation under conscious sedation and topical airway anesthesia, in an 11-year-old child with Goldenhar syndrome and ASD.