Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: A randomized, double-blind, placebo-controlled trial

Background. Patients with reactive airways are at risk for adenosine-induced bronchocon-striction, mediated via A_2B and/or A₃ adenosine receptors. Methods and Results. To examine the effects of regadenoson, a selective adenosine A_2A receptor agonist, on airway resistance, we conducted a randomized, double-blind, placebo-controlled crossover trial in asthmatic patients with a positive adenosine monophosphate challenge test. The mean ratio of the forced expiratory volume in 1 second (FEV₁) at each tested time point relative to the baseline FEV₁ was significantly higher after treatment with regadenoson compared with placebo from 10 to 60 minutes after treatment. One patient had a substantial but asymptomatic FEV₁ reduction (−36.2%) after regadenoson that reversed spontaneously. The most common adverse events with regadenoson were tachycardia (66%), dizziness (53%), headache (45%), and dyspnea (34%). The mean heart rate significantly increased with regadenoson (maximum of +10.4 beats/min) versus placebo. Conclusions. In this pilot safety study of 48 patients with mild or moderate asthma who had bronchial reactivity to adenosine monophosphate, regadenoson was safe and well tolerated. CV Therapeutics provided financial assistance for this study.     

Ciliary activity and pollution

The mucociliary clearance is an important part of the nonspecific defense mechanism of the human airways. Coordinated beats of cilia in the nose, trachea, and bronchi propel the mucous layer toward the pharynx, and with it inhaled microorganisms and other particles captured in the mucus. Normal function of this system depends on the efficacy of the ciliary beating and the properties of mucus. Primary ciliary dyskinesia—a congenital respiratory disease characterized by ultrastructural defects and motility disturbances of cilia—has provided us with valuable information about the role the mucociliary function plays in the protection against harmful agents in the inhaled air. Secondary ciliary dyskinesia is described in inflammatory disorders of the respiratory tract, but also some components in air pollution results in malfunction of cilia, damage of ciliated epithelium, or alteration in the mucus. This review will focus on investigations found in the literature concerning the influence of pollutants on ciliary activity. The methods applied will be evaluated.     

Nasal nitric oxide measurements before and after repeated humming maneuvers

BACKGROUND: It has been recently shown that humming greatly increases nasal nitric oxide (NO). This is most likely owing to a rapid washout of sinus NO caused by the oscillating sound waves. During repeated humming manoeuvres nasal NO gradually decreases, likely because NO accumulated in the sinuses is washed out. AIM: We studied whether humming before measurements would affect nasally exhaled NO. MATERIALS AND METHODS: NO output was measured by the chemiluminescence technique in orally and nasally exhaled air in 38 subjects: 18 healthy subjects (HS), 15 subjects with allergic rhinitis (AR) and five subjects with allergic nasal polyposis (AP). Each subject performed a NO measurement during quiet nasal exhalation either preceded by a period of silence/free speaking or immediately after five consecutive humming manoeuvres (posthumming). RESULTS: Mean nasal NO output (95% CI) after a period of silence/free speaking was 231 nL min-1 (178-284) in HS, 434 nL min-1 (347-522) in AR (P < 0.001) and 262 nL min-1 (163-361) in AP. Post-humming nasal NO output was 16% (5 to 50%) lower in HS and 14% (1 to 49%) lower in AR, while it remained unchanged in AP subjects. Intra-subject coefficient of variation of quiet nasal exhalation was 12% in HS, 13% in AR and 5% in AP. Post humming intraindividual coefficient of variation significantly decreased in both HS and AR, but it did not change in AP. CONCLUSIONS: Nasal NO levels measured immediately after repeated humming manoeuvres are consistently lower and more reproducible than nasal NO levels measured after a period of silence or free speaking. Repeated humming effectively empties the sinuses, thereby probably minimizing the normal contribution from the sinuses to nasal NO. This may be useful to better estimate NO output from the nasal cavity mucosa in health and disease.     

Clinical assessment of awake endotracheal intubation using the lightwand technique alone in patients with difficult airways

Background There is few study to determine whether the use of the lightwand technique alone could achieve effective, safe and successful awake endotracheal intubation （ETI）, therefore we designed a prospective clinical study to systematically evaluate the feasibility, safety and efficacy of awake ETI using the lightwand alone in patients with difficult airways.
Methods Seventy adult patients with difficult airways were enrolled in this study. After the desired sedation with fentanyl and midazolam, airway topical anesthesia was performed with 9 ml of 2% lidocaine, which were in order sprayed in three aliquots at 5 minutes intervals into the supraglottic （two doses） and laryngotracheal areas （one dose） using a combined unit of the lightwand and MADgic atomizer. After airway topical anesthesia, awake ETI was performed using a Lightwand. Subjective assessments by patients and operators using the visual analogue scores （VAS）, and objective assessments by an independent investigator using patients＇ tolerance and reaction scores, coughing severity, intubating conditions and cardiovascular variables were taken as the observed parameters.
Results Of 210 airway sprays, 197 （93.8%） were successfully completed on the first attempt. The total time for airway spray was （14.6±1.5） minutes. During airway topical anesthesia, the average patients＇ tolerance scores were 1.7-2.3. After airway topical anesthesia, the mean VAS for discomfort levels that the patients reported was 6.5. Also airway topical anesthesia procedure was rated as acceptable and no discomfort by 94.3% of patients. The lightwand-guided awake ETI was successfully completed on first attempt within 29 seconds in all patients. During awake ETI, patients＇ reaction and coughing scores were 1.9 and 1.6, respectively. All patients exhibited excellent or acceptable intubating conditions. Cardiovascular monitoring revealed that changes of systolic blood pressure and heart rate at each stage of airway manipulations were less than 20% of baseline values. The postoperative follow-up showed that 95.7% of patients had no recall or slight memories of all airway instrumentation. The incidence of postoperative mild airway complications was 38.6%.
Conclusion Alone use of the lightwand technique can achieve effective, safe and successful awake ETI in patients with difficult airways.     

Fluid flow in distensible vessels

1. Flow in single vascular conduits is reviewed, divided into distended and deflated vessels. 2. In distended vessels with pulsatile flow, wave propagation and reflection dominate the spatial and temporal distribution of pressure, determining the shape, size and relative timing of measured pressure waveforms, as well as the instantaneous pressure gradient everywhere. Considerable research has been devoted to accessing the information on pathological vascular malformations contained in reflected waves. Slow waves of contraction of vessel wall muscle, responsible for transport of oesophageal, ureteral and gut contents, have also been modelled. 3. The pressure gradient in a vessel drives the flow. Flow rate can be predicted both analytically and numerically, but analytical theory is limited to idealized geometry. The complex geometry of biological system conduits necessitates computation instead. Initially limited to rigid boundaries, numerical methods now include fluid-structure interaction and can simultaneously model solute transport, thus predicting accurately the environment of the mechanosensors and chemosensors at vessel surfaces. 4. Deflated vessels display all phenomena found in distended vessels, but have additional unique behaviours, especially flow rate limitation and flow-induced oscillation. Flow rate limitation is widespread in the human body and has particular diagnostic importance in respiratory investigation. Because of their liquid lining, the pulmonary airways are also characterized by important two-phase flows, where surface tension phenomena create flows and determine the patency and state of collapse of conduits. 5. Apart from the vital example of phonation, sustained self-excited oscillation is largely avoided in the human body. Where it occurs in snoring, it is implicated in the pathological condition of sleep apnoea.     

The treatable traits approach to adults with obstructive airways disease in primary and secondary care

The treatable traits approach is based on the recognition that the different clinical phenotypes of asthma and chronic obstructive airways disease (COPD) are a heterogeneous group of conditions with different underlying mechanisms and clinical manifestations, and that the identification and treatment of the specific clinical features or traits facilitates a personalised approach to management. Fundamentally, it recognises two important concepts. Firstly, that treatment for obstructive lung disease can achieve better outcomes if guided by specific clinical characteristics. Secondly, that in patients with a diagnosis of asthma, and/or COPD, poor respiratory health may also be due to numerous overlapping disorders that can present with symptoms that may be indistinguishable from asthma and/or COPD, comorbidities that might require treatment in their own right, and lifestyle or environmental factors that, if addressed, might lead to better control rather than simply increasing airways directed treatment. While these concepts are well accepted, how best to implement this personalised medicine approach in primary and secondary care within existing resource constraints remains uncertain. In this review, we consider the evidence base for this management approach and propose that the priority now is to assess different prototype templates for the identification and management of treatable traits in both asthma and COPD, in primary, secondary and tertiary care, to provide the evidence that will guide their use in clinical practice in different health care systems.     

Small Airways Dysfunction in Asthma: Evaluation and Management to Improve Asthma Control

The small airways have been neglected for many years, but interest in the topic has been rekindled with recent advances in measurement techniques to assess this region and also the ability to deliver therapeutics to the distal airways. Current levels of disease control in asthmatic patients remain poor and there are several contributory factors including; poor treatment compliance, heterogeneity of asthma phenotypes and associated comorbidities. However, the proposition that we may not be targeting all the inflammation that is present throughout the whole respiratory tree may also be an important factor. Indeed decades ago, pathologists and physiologists clearly identified the importance of small airways dysfunction in asthmatic patients. With improved inhaler technology to deliver drug to target the whole respiratory tree and more sensitive measures to assess the distal airways, we should certainly give greater consideration to treating the small airway region when seeing our asthmatic patients in clinic. The aim of this review is to address the relevance of small airways dysfunction in the daily clinical management of patients with asthma. In particular the role of small particle aerosols in the management of patients with asthma will be explored.