The use of rhDNAse in severely ill, non-intubated adult asthmatics refractory to bronchodilators: A pilot study
ABSTRACT Mucous plugging is associated with fatal asthma and may have a causative role for non-fatal cases of severe acute asthma. However, mucolytic agents have not been found effective in reversing the obstruction of acute asthma. We test the hypothesis that rhDNAse, an agent that reduces viscoelasticity of sputum in patients with cystic fibrosis, has a therapeutic role in acute asthma.
Symptomatic asthmatics aged 18-55 years presenting to an Emergency Department with an FEV(1) < 60% predicted after 2 nebulized albuterol and ipratropium treatments were included. Patients were randomized into one of three nebulized rhDNAse treatment groups of 2.5, 5.0 or 7.5 mg, or placebo. Standardized bronchodilator therapy was continued throughout the protocol and the FEV(1) at 6 h was the primary study endpoint.
50 patients were enrolled. There were no significant differences in FEV(1)% predicted between the rhDNAse and placebo patients at any of the post-randomization time points. The dose of rhDNAse administered did not influence response. In a post-hoc stratification, patients with the lowest pre-randomization FEV(1) tended to improve more from rhDNAse, particularly at times 60 and 120 min post-randomization.
In this pilot study rhDNAse did not cause clinical improvement among severely ill adults refractory to standardized care. The observed trend to higher FEV(1) among the most severely obstructed patients is an exploratory finding that may warrant further study. This clinical trial was registered as NCT00169962 under the name "Study of Pulmozyme to Treat Severe Asthma Episodes".
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ABSTRACT: Aim. The extent to which mucolytics are utilised in mechanically ventilated asthmatic children is unknown. We sought to establish current practice in the United Kingdom (UK) including choice of mucolytic, dose, and frequency of utilisation. Methods. A national electronic survey was distributed to UK consultants during April and May 2014. We were able to identify 168 PICU consultants at 25 institutions to whom we were able to electronically distribute a survey, representing an estimated 81% of UK NHS PICU consultants. Results. Replies were received from 87 consultants at 21 institutions (%). Recombinant human DNase (rhDNase) does get administered by 63% of clinicians, with 54% and 19% that administer hypertonic saline or N-acetylcysteine, respectively. Of those that do administer rhDNase the majority (48%) dilute it with 0.9% saline and blindly administer it, whereas 35% administer rhDNase under bronchoscopic guidance and 17% judge the necessity for bronchoscopy according to clinical severity. 25 respondents described 7 different methods to calculate rhDNase dose. A majority (87%) of respondents expressed an interest to consider enrolling patients into an RCT that evaluates rhDNase. Conclusion. Significant variation exists regarding the necessity for mucolytics, choice of agent, optimal route, and dose in intubated asthmatic children.Critical care research and practice 02/2015; 2015:1-5. DOI:10.1155/2015/396107
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ABSTRACT: Inhaled anticholinergics given in addition to β2-agonists are effective in reducing hospital admissions in children presenting to the emergency department with a moderate to severe asthma exacerbation. It seems logical to assume a similar beneficial effect in children hospitalised for an acute asthma exacerbation.Cochrane database of systematic reviews (Online) 07/2014; 7(7):CD010283. DOI:10.1002/14651858.CD010283.pub2 · 5.94 Impact Factor
Article: The Acute Management of Asthma[Show abstract] [Hide abstract]
ABSTRACT: Patients presenting to the emergency department (ED) or clinic with acute exacerbation of asthma (AEA) can be very challenging varying in both severity and response to therapy. High-dose, frequent or continuous nebulized short-acting beta2 agonist (SABA) therapy that can be combined with a short-acting muscarinic antagonist (SAMA) is the backbone of treatment. When patients do not rapidly clinically respond to SABA/SAMA inhalation, the early use of oral or parenteral corticosteroids should be considered and has been shown to impact the immediate need for ICU admission or even the need for hospital admission. Adjunctive therapies such as the use of intravenous magnesium and helium/oxygen combination gas for inhalation and for driving a nebulizer to deliver a SABA and or SAMA should be considered and are best used early in the treatment plan if they are likely to impact the patients' clinical course. The use of other agents such as theophylline, leukotriene modifiers, inhaled corticosteroids, long-acting beta2 agonist, and long-acting muscarinic antagonist currently does not play a major role in the immediate treatment of AEA in the clinic or the ED but is an important therapeutic option for physicians to be aware of and to consider initiating at the time of discharge from clinic, hospital, or ED to reduce later clinical worsening and readmission to the ED and hospital. A comprehensive summary is provided of the currently available respiratory pharmaceuticals approved for asthma and other airway syndromes. Clinicians must be prepared to use the entire spectrum of medications available for the treatment of acute asthma exacerbations and the agents that should be initiated to prevent worsening or additional exacerbations. They need to be familiar with the major potential drug toxicities associated with their use.Clinical Reviews in Allergy & Immunology 09/2014; 48(1). DOI:10.1007/s12016-014-8448-5 · 4.73 Impact Factor