An open, randomized, parallel-group study was conducted to investigate whether asthmatic patients, considered adequately treated with a corticosteroid and/or short-acting beta 2-agonist via pressurized metered-dose inhaler (pMDI), could be transferred to a corresponding nominal dose of budesonide and/or terbutaline via Turbuhaler, an inspiratory flow-driven multidose dry powder inhaler (Astra Draco; Lund, Sweden), without a decrease in the effect of treatment. One thousand four patients (555 women; mean age, 44 years; mean peak expiratory flow [PEF], 102% predicted normal value) were randomized and treated with either pMDI (current therapy) or Turbuhaler for 52 weeks. The variables studied were asthma-related events, morning PEF, and inhaler-induced clinical symptoms. Asthma-related events were defined in two ways: (1) sum of health-care contacts plus doublings or additions of steroids, and (2) number of 2 consecutive days with PEF less than 80% of baseline. Baseline was obtained from a 2-week run-in period while receiving previous therapy. No statistically significant difference was found in asthma-related events according to definition 1. According to definition 2, there was a statistically significant difference between the groups in favor of Turbuhaler (p = 0.008). The mean number of events was 1.7 with Turbuhaler and 2.2 with pMDI. The mean number of weeks per patient with a PEF less than 90% of baseline was 4.5 with Turbuhaler compared with 6.0 with pMDI (p = 0.002). The sum of inhaler-induced symptoms after 1 year of use was statistically significantly lower with Turbuhaler (0.40) than with pMDI (0.75) (p = 0.0001). In conclusion, budesonide and terbutaline in Turbuhaler offered a superior alternative to corticosteroids and bronchodilators delivered by pMDIs in the maintenance treatment of asthma.
Anaesthesiologists from Oslo University Hospital have transported patients with severe oxygenation failure with inhaled nitric oxide (usually 20?ppm) from other hospitals to a tertiary care centre since 2002 in an effort to reduce the number of patients that otherwise would require transport with ongoing extracorporeal membrane oxygenation. The aim of this study was to evaluate the patient safety during transport with inhaled nitric oxide.
All patient transports with ongoing nitric oxide treatment undertaken from 2003 to 2012 were identified in the transport database. The frequency of adverse events and their impact on patient safety were studied in addition to response to inhaled nitric oxide and adjusted intensive care treatment and time aspects of the transports. Information about in-hospital treatment and survival were extracted from the hospital patient records.
Adverse events were recorded in 12 of the 104 transports. Seven of the adverse events were due to malfunctioning technical equipment, three were related to medication other than the inhaled nitric oxide and two were related to ventilation. No adverse events resulted in permanent negative patient consequences or in discontinuation of the transport. Out of 104 patients, 79 responded to treatment with inhaled nitric oxide and other treatment changes by an increase in oxygen saturation of more than 5%. The 30-day mortality was 27% in the group transported with inhaled nitric oxide.
Transporting patients on inhaled nitric oxide is an alternative in selected patients who would otherwise require extracorporeal membrane oxygenation during transport.
We wanted to study the effects of a 600 micrograms inhaled salbutamol dose on the cardiovascular and respiratory autonomic nervous regulation in eight children suffering from bronchial asthma.
In this randomized, double-blind, placebo-controlled, crossover study we continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R-R interval (the time between successive heart beats) and SAP variabilities were assessed by using spectral analysis. Baroreflex sensitivity was assessed by using cross-spectral analysis.
Salbutamol significantly decreased the total and low frequency (LF) variability of R-R intervals as well as the high frequency (HF) variability of R-R intervals and of SAP. Salbutamol significantly increased the LF/HF ratio of R-R intervals and of SAP, minute ventilation, heart rate and forced pulmonary function in comparison with placebo. The weight of the subjects significantly correlated positively with baroreflex sensitivity and negatively with heart rate after the salbutamol inhalation.
We conclude that the acute salbutamol inhalation decreases cardiovagal nervous responsiveness, increases sympathetic dominance in the cardiovascular autonomic balance, and has a tendency to decrease baroreflex sensitivity in addition to improved pulmonary function.
BACKGROUND: Adjustable maintenance dosing with budesonide/formoterol in a single inhaler (Symbicort, AstraZeneca, Lund, Sweden) may provide a convenient means of maintaining asthma control with the minimum effective medication level. OBJECTIVES: To compare adjustable and fixed maintenance dosing regimens of budesonide/formoterol in asthma. METHODS: This was an open-label, randomized, parallel-group, multicentre, Canadian study of asthma patients (aged 12 years or older, postbronchodilator forced expiratory volume in 1 s 70% or greater of predicted normal). Following a one-month run-in on budesonide/formoterol (100/6 mg or 200/6 mg metered doses, two inhalations twice daily), 995 patients were randomly assigned either to continue on this fixed dosing regimen or to receive budesonide/formoterol adjustable dosing (step down to one inhalation twice daily if symptoms were controlled or temporarily step up to four inhalations twice daily for seven or 14 days if asthma worsened). The primary efficacy variable was the occurrence of exacerbations (requiring oral or inhaled corticosteroids, emergency department treatment, serious adverse events or added maintenance therapy because of asthma). RESULTS: With adjustable dosing, significantly fewer patients experienced exacerbations compared with fixed dosing (4.0% versus 8.9%, P=0.002; number needed to treat=21 [95% CI 13 to 59]). Patients required 36% fewer overall doses of budesonide/formoterol (2.5 versus 3.9 inhalations/day, P
Many investigations suggest that a high degree of air-borne pollution increases the prevalence of diseases like asthma and eczema. SÃ¸r-Varanger Municipality in Finnmark County in the north of Norway receives much air-borne pollution from domestic industry and from the metallurgic industry on the Kola peninsula in North-Western Russia. We have investigated indirect parameters of morbidity caused by asthma and eczema by analyzing data on drug consumption and hospital admissions. In SÃ¸r-Varanger there is high consumption of corticosteroids for dermatological use. Consumption of anti-asthmatic drugs and number of admissions to hospital for asthma and eczema were no higher than expected. We suspect that air-borne pollution, particularly the heavy metal nickel, increases the prevalence and perhaps worsens the degree of eczema in SÃ¸r-Varanger.
Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence-based guidelines, it is often justified by the belief in a subgroup effect in individuals developing atopic disease. We aimed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction, atopic eczema, or allergic sensitisation.
In the randomised, double-blind, multicentre Bronchiolitis ALL trial, 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay. Randomisation was done centrally, and the two study medications (20 mg/mL racemic epinephrine or 0.9% saline) were prepared in identical bottles. The dose given depended on the infant's weight: 0.10 mL, less than 5 kg; 0.15 mL, 5-6.9 kg; 0.2 mL, 7-9.9 kg; and 0.25 mL, 10 kg or more; all dissolved in 2 mL of 0.9% saline before nebulisation. The primary outcome was the length of hospital stay. In this follow-up study, 294 children were reinvestigated at 2 years of age with an interview, a clinical examination, and a skin prick test for 17 allergens, determining bronchial obstruction, atopic eczema, and allergic sensitisation, on which subgroup analyses were done. Analyses were done by intention to treat. The trial has been completed and is registered at ClinicalTrials.gov (number NCT00817466) and EUDRACT (number 2009-012667-34).
Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years (143 [48.6%] of 294 patients; p(interaction)=0.40). However, the presence of atopic eczema or allergic sensitisation by the age of 2 years (n=77) significantly interacted with the treatment effect of inhaled epinephrine (p(interaction)=0.02); the length of stay (mean 80.3 h, 95% CI 72.8-87.9) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years (-19.9 h, -33.1 to -6.3; p=0.003). No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years (+16.2 h, -11.0 to 43.3; p=0.24).
Contrary to our hypothesis, hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema, allergic sensitisation, or recurrent bronchial obstruction. The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases.
The aerodynamic properties of 99mTc radiolabeled carrier-free terbutaline sulphate (TBS) have been thoroughly investigated following delivery by Turbuhaler (AstraZeneca Lund, Sweden). A full and detailed radiolabeling procedure is also reported. The in vitro radiolabel validation was performed to determine whether TBS radiolabeled in this way would be representative of the commercially available product Bricanyl Turbuhaler during clinical trials. The results indicated that variations in aerodynamic properties had been introduced and that the radiolabel would slightly underestimate the fine particle fraction of Bricanyl, but would nonetheless act as a suitable marker in vivo. Assumptions regarding the aerodynamic properties of doses likely to be received by clinical trial subjects were also examined. This has been achieved by extending the validation procedures beyond those usually reported to include dose number, time, and homogeneity dependent studies. It was found that doses extracted for testing purposes and simulated patient doses extracted shortly afterward had similar properties. Doses extracted 2 h after initial testing also had similar properties to the test doses. These results suggested that data from the test doses could be used for quality control purposes, would be representative of the doses to be received by clinical trial subjects, and that a short delay between initial testing and trial subject inhalation would be acceptable.
Bronchodilator aerosols are commonly delivered through nebulizers or metered dose inhalers (MDI) to treat bronchospasm. Although the clinical results obtained with both these devices are comparable, the use of MDI offers several advantages like lower drug dose, reduced risk of complications, reliability of dosing, ease of administration, less personnel time and reduced cost. However, in non-intubated, spontaneously breathing patients, the amount of drug inhaled depends on the coordination of the inspiratory phase and delivery of the drug. In severely dyspnoeic or disoriented patients in the casualty department or intensive care settings, this is often not possible. Valved spacers and breath-actuated inhalers may not be easily available in such situations. Also, the spacer devices cannot be connected to the anatomical facemask and the need to discontinue oxygenation for aerosol delivery further limits their use.
Until recently, there have been few clinical algorithms for the management of patients with COPD. Current evidence-based clinical management guidelines can appear to be complex, and they lack clear step-by-step instructions. For these reasons, we chose to create a simple and practical clinical algorithm for the management of patients with COPD, which would be applicable to real-world clinical practice, and which was based on clinical symptoms and spirometric parameters that would take into account the pathophysiological heterogeneity of COPD. This optimized algorithm has two main fields, one for nonspecialist treatment by primary care and general physicians and the other for treatment by specialized pulmonologists. Patients with COPD are treated with long-acting bronchodilators and short-acting drugs on a demand basis. If the forced expiratory volume in one second (FEV1) is =50% of predicted and symptoms are mild, treatment with a single long-acting muscarinic antagonist or long-acting beta-agonist is proposed. When FEV1 is 3%; 2) neutrophilic endotype with peripheral blood neutrophilia >60% or green sputum; or 3) pauci-granulocytic endotype. It is hoped that this simple, optimized, step-by-step algorithm will help to individualize the treatment of COPD in real-world clinical practice. This algorithm has yet to be evaluated prospectively or by comparison with other COPD management algorithms, including its effects on patient treatment outcomes. However, it is hoped that this algorithm may be useful in daily clinical practice for physicians treating patients with COPD in Russia.
Cites: Eur Respir J. 2013 Apr;41(4):993-5 PMID 23543648
Low-rate smoking patterns are common, but their pulmonary effects remain poorly known. The study hypothesis was that any level of daily smoking may cause chronic obstructive pulmonary disease (COPD). We investigated the association between longitudinal smoking patterns and COPD using logistic regressions and survival models adjusted for multiple covariates. Data from Finnish Twin Cohort surveys were used. Participants (n = 21,609) were grouped into categories describing 1981 smoking and change in smoking during 1975-1981. Light smoking was defined as