Integrin α9β1 in airway smooth muscle suppresses exaggerated airway narrowing

Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α9β1 on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking integrin α9β1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α9β1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α9β1 or treated with integrin α9β1-blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α9β1. Therefore, integrin α9β1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma.     

Is surgical airway necessary for airway management in deep neck infections and Ludwig angina?

Background

Deep neck infections are potentially life-threatening conditions because of airway compromise. Management requires early recognition, antibiotics, surgical drainage, and effective airway control. The Surgical Education and Self-Assessment Program 12 states that awake tracheostomy is the treatment of choice for these patients.

Hypothesis

With advanced airway control techniques such as retrograde intubation, GlideScope, and fiberoptic intubation, surgical airway is not required.

Design

A retrospective analysis of all deep neck abscesses treated from December1999 to July 2006 was performed.

Methods

All patients who underwent urgent or emergent surgery for Ludwig angina and submental, submandibular, sublingual, and parapharyngeal abscesses (Current Procedural Terminology codes 41015, 41016, 41017, 42320, and 42725) were included in our review. Charts were studied for age, presence of true Ludwig angina, presence of airway compromise, airway management, morbidity/mortality, and the requirement for surgical airway.

Results

Of 29 patients, 6 (20%) had symptoms consistent with true Ludwig angina. Nineteen (65.5%) had evidence of airway compromise. Eight (42%) of these 19 patients required advanced airway control techniques. No patient required a surgical airway, and no mortality resulted from airway compromise. Advance airway control techniques were required more often in patients with airway compromise (P < .05).

Conclusion

Treatment of Ludwig angina and deep neck abscesses requires good clinical judgment. Patients with deep neck infections and symptoms of airway compromise may be safely managed with advanced airway control techniques.     

Allergen-specific Th1 cells fail to counterbalance Th2 cell–induced airway hyperreactivity but cause severe airway inflammation

Allergic asthma, which is present in as many as 10% of individuals in industrialized nations, is characterized by chronic airway inflammation and hyperreactivity induced by allergen-specific Th2 cells secreting interleukin-4 (IL-4) and IL-5. Because Th1 cells antagonize Th2 cell functions, it has been proposed that immune deviation toward Th1 can protect against asthma and allergies. Using an adoptive transfer system, we assessed the roles of Th1, Th2, and Th0 cells in a mouse model of asthma and examined the capacity of Th1 cells to counterbalance the proasthmatic effects of Th2 cells. Th1, Th2, and Th0 lines were generated from ovalbumin (OVA)-specific T-cell receptor (TCR) transgenic mice and transferred into lymphocyte-deficient, OVA-treated severe combined immunodeficiency (SCID) mice. OVA-specific Th2 and Th0 cells induced significant airway hyperreactivity and inflammation. Surprisingly, Th1 cells did not attenuate Th2 cell–induced airway hyperreactivity and inflammation in either SCID mice or in OVA-immunized immunocompetent BALB/c mice, but rather caused severe airway inflammation. These results indicate that antigen-specific Th1 cells may not protect or prevent Th2-mediated allergic disease, but rather may cause acute lung pathology. These findings have significant implications with regard to current therapeutic goals in asthma and allergy and suggest that conversion of Th2-dominated allergic inflammatory responses into Th1-dominated responses may lead to further problems.     

What does airway resistance tell us about lung function?

Spirometry is considered the primary method to detect the air flow limitation associated with obstructive lung disease. However, air flow limitation is the end-result of many factors that contribute to obstructive lung disease. One of these factors is increased airway resistance. Airway resistance is traditionally measured by relating air flow and driving pressure using body plethysmography, thus deriving airway resistance (R(aw)), specific airway resistance (sR(aw)), and specific airway conductance (sG(aw)). Other methods to measure airway resistance include the forced oscillation technique (FOT), which allows calculation of respiratory system resistance (R(RS)) and reactance (X(RS)), and the interrupter technique, which allows calculation of interrupter resistance (R(int)). An advantage of these other methods is that they may be easier to perform than spirometry, making them particularly suited to patients who cannot perform spirometry, such as young children, patients with neuromuscular disorders, or patients on mechanical ventilation. Since spirometry also requires a deep inhalation, which can alter airway resistance, these alternative methods may provide more sensitive measures of airway resistance. Furthermore, the FOT provides unique information about lung mechanics that is not available from analysis using spirometry, body plethysmography, or the interrupter technique. However, it is unclear whether any of these measures of airway resistance contribute clinically important information to the traditional measures derived from spirometry (FEV(1), FVC, and FEV(1)/FVC). The purpose of this paper is to review the physiology and methodology of these measures of airway resistance, and then focus on their clinical utility in relation to each other and to spirometry.     

Traumatic retropharyngeal hematoma—A cause of acute airway obstruction

Blunt trauma causing a retropharyngeal hematoma without an associated cervical fracture is a relatively rare occurrence. This article presents the case of a patient with airway compromise from a retropharyngeal hematoma, and discusses the diagnosis, airway management, and treatment of this condition.     

Is tracheostomy suitable for securing airway after facial firearm injuries?

BACKGROUND:

Head and neck region have many vital structures, and facial firearm injuries (FFIs) more likely lead to life-threatening situations than other body injuies. These injuries have high potential of airway compromise associated with significant morbidity and mortality.

METHODS:

We describe an 11-year-old boy who had received tracheostomy after a FFI complicated with pneumothorax and subcutaneous emphysema 8 hours after the procedure. The patient was treated at the Department of Emergency and Critical Care, Gazi University School of Medicine, Turkey.

RESULTS:

The patient was discharged without any complications from the Critical Care Unit after treatment for five days.

CONCLUSIONS:

Airway management is of utmost importance in resuscitation of FFI, but it is always difficult to secure via the orotracheal route due to the deformed facial structures. Tracheostomy is an option for airway management in FFI affecting head and neck region. However, tracheostomy may be associated with life-threatening complications, which should be closely monitored with early intervention.KEY WORDS: Airway obstruction, Emphysema, Firearms, Pediatrics, Tracheostomy     

Is digital intubation an option for emergency physicians in definitive airway management?

OBJECTIVES: This study was designed to determine whether digital intubation is a valid option for definitive airway control by emergency physicians. METHODS: Digital intubation was performed by 18 emergency medicine residents and 4 staff emergency medicine physicians on 6 different cadavers. Placement was confirmed by direct laryngoscopy. The total time for all attempts used, as well as the number of attempts, was recorded. Each participant attempted intubation on all 6 cadavers. RESULTS: For 5 of the 6 cadavers, successful intubation occurred 90.9% of the time (confidence interval [CI], 85.5%-96.3%) for all participants. The average number of attempts for these 5 cadavers was 1.5 (CI, 1.4-1.7), and the average time required for success or failure was 20.8 seconds (CI, 16.9-24.8). The sixth cadaver developed soft tissue damage and a false passage near the vocal cords resulting in multiple failed attempts. CONCLUSIONS: Although the gold standard for routine endotracheal intubation remains to be direct laryngoscopy, its effectiveness in certain situations may be limited. We believe that digital intubation provides emergency physicians with another option in securing the unprotected airway.     

Does the type of out-of-hospital airway interfere with other cardiopulmonary resuscitation tasks?

BACKGROUND: Out-of-hospital rescuers often perform tracheal intubation (TI) prior to other cardiopulmonary resuscitation (CPR) interventions. TI is a complex and error-prone procedure that may interfere with other key resuscitation tasks. We compared the effects of TI versus esophageal tracheal combitube (ETC) insertion on the accomplishment of other interventions during simulated cardiopulmonary resuscitation. METHODS: In this prospective trial using a human simulator, two-paramedic teams simulated resuscitation of a ventricular fibrillation cardiopulmonary arrest using standard Advanced Cardiac Life Support guidelines. In each of two trials, teams used either TI or ETC as the primary airway device. Following delivery of three rescue shocks, we measured time intervals to successful airway placement, intravenous (IV) line insertion, drug administration, delivery of fourth rescue shock and completion of all four tasks. We also measured the total time without chest compressions. We compared task completion times using non-parametric statistics (Wilcoxon signed-ranks test) with a Bonferroni-adjusted p-value of 0.008. RESULTS: Twenty teams each completed two scenarios. Participants required a median of 172.5 s (IQR: 146.5-225.5) to accomplish all four tasks. Elapsed time to airway placement was significantly less for ETC than TI (median difference 26.5 s (IQR 13-44.5), p=0.002). Time without chest compressions was less for ETC than TI (median difference 8.5 s (IQR 2.5-23.5), p=0.005). There were no differences between ETC and TI in times to IV placement (median difference 23.5 s (IQR -20 to 61), p=0.11), drug delivery (39.5 s (IQR -18 to 63), p=0.07), delivery of fourth rescue shock (39.5 s (IQR -21.5 to 87.5), p=0.07) or completion of all four tasks (33 s (IQR -11 to 74.5), p=0.08). CONCLUSION: Compared with TI, ETC reduced time to airway placement and time without chest compressions, but did not affect elapsed times to accomplish other interventions. Additional time differences may be realized if translated to clinical out-of-hospital conditions.     

Chemokine-mediated angiogenesis: an essential link in the evolution of airway fibrosis?

Angiogenesis may be an important factor in the development of fibrotic lung disease. Prior studies have strongly suggested a role for angiogenic vascular remodeling in pulmonary fibrosis, and emerging evidence indicates that new vessel formation is critical in airway fibrosis. Bronchiolitis obliterans syndrome is a fibrotic occlusion of distal airways that is largely responsible for the morbidity and mortality of patients after lung transplantation. In this issue, Belperio et al. demonstrate a role for CXC chemokine receptor 2 in the regulation of angiogenesis-mediated airway fibroproliferation. By integrating an understanding of neovascularization into the study of events that occur between inflammation and fibrosis, it becomes increasingly possible to rationally design therapies that can halt conditions of maladaptive fibrosis.     

Continuous positive airway pressure ventilation with helmet in infants under 1 year

Objective  

To report the feasibility of helmet use in infants between 1 and 12 months old with acute respiratory failure.     

The experimental studies of Heliox decreasing airway resistance and improving pulmonary effective ventilation

AIM：The study evaluated the effects of breathing helium-oxygen (79% heliox and 21% oxygen) on respiratory insufficiency by way of experimental and clinical observations. METHODS:Six mongrel dogs were randomly inspired air or heiox after dripping 2% methacholine in tracheas controlled by 900C ventilator.During the experimental course, respiratory mechanical limits, hemodynamic index and blood gas values were observed. Six ventilated patients with COPD in the respiratory intensive care unit inspired heliox, and the data of respiratory mechanics were recorded. RESULTS:The results demonstrate that heliox can reduced airway resistance, airway pressure,and work of breathing, improve lung effective compliance,but heliox has no side effects on pulmonary circulation and systemic circulation. Heliox improves oxygen diffusion and CO2 climinating. CONCLUSION:Breathing heliox is one of the effective ways for patients with severe obstructive pulmonary diseases.