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Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma.


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The effect on Paco(2) of high concentration oxygen therapy when administered to patients with severe exacerbations of asthma is uncertain.

Methods 106 patients with severe exacerbations of asthma presenting to the Emergency Department were randomised to high concentration oxygen (8 l/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93% and 95%) for 60 min. Patients with chronic obstructive pulmonary disease or disorders associated with hypercapnic respiratory failure were excluded. The transcutaneous partial pressure of carbon dioxide (Ptco(2)) was measured at 0, 20, 40 and 60 min. The primary outcome variable was the proportion of patients with a rise in Ptco(2) ≥4 mm Hg at 60 min.

Results The proportion of patients with a rise in Ptco(2) ≥4 mm Hg at 60 min was significantly higher in the high concentration oxygen group, 22/50 (44%) vs 10/53 (19%), RR 2.3 (95% CI 1.2 to 4.4, p<0.006). The high concentration group had a higher proportion of patients with a rise in Ptco(2) ≥8 mm Hg, 11/50 (22%) vs 3/53 (6%), RR 3.9 (95% CI 1.2 to 13.1, p=0.016). All 10 patients with a final Ptco(2) ≥45 mm Hg received high concentration oxygen therapy, and in five there was an increase in Ptco(2) ≥10 mm Hg.

Conclusion High concentration oxygen therapy causes a clinically significant increase in Ptco(2) in patients presenting with severe exacerbations of asthma. A titrated oxygen regime is recommended in the treatment of severe asthma, in which oxygen is administered only to patients with hypoxaemia, in a dose that relieves hypoxaemia without causing hyperoxaemia. Clinical trial number ACTRN12607000131459.

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Neural respiratory drive as a physiological biomarker to monitor change during acute exacerbations of COPD.


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Acute exacerbations of chronic obstructive pulmonary disease have a significant negative impact on both patients and healthcare systems. Currently, there are no physiological biomarkers that effectively monitor clinical change or predict respiratory readmission. Acute exacerbations impose a change in the respiratory muscle load-capacity-drive relationship.

It was hypothesised that lack of a fall in neural respiratory drive would identify patients at risk of treatment failure and early hospital readmission.

Methods An observational study was performed at two UK teaching hospitals. Routine clinical physiological parameters and neural respiratory drive index (NRDI), calculated as the product of second intercostal space parasternal electromyography (EMG) activity normalised to the peak EMG activity during a maximum inspiratory sniff manoeuvre and respiratory rate, were recorded daily from admission to discharge.

Results 30 acutely unwell patients of mean (SD) age 72 (10) years, forced expiratory volume in 1 s 0.60 (1.65) l, NRDI 455 (263) AU and median length of stay 6 days were studied. Changes in NRDI correlated with changes in Borg score (r=+0.60; p<0.001), discriminated between patients deemed to have clinically improved rather than deteriorated (mean difference 339 AU; 95% CI 234 to 444; p<0.001) and identified those patients readmitted within 14 days (mean difference 203 AU; 95% CI 39 to 366; p=0.017).

Conclusions NRDI is a feasible clinical physiological parameter in patients with an acute exacerbation of chronic obstructive pulmonary disease and can provide useful information on treatment response and risk of readmission.

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Chronic Urticaria: Etiology and Natural Course in Children.


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Chronic spontaneous urticaria (CSU) in childhood is infrequent, and information about the disease in children is limited. We attempted to investigate its etiologic factors, natural course, and predictors of prognosis.

Methods: All children aged ≤18 years followed for CSU during an 8-year period were analyzed retrospectively, and the final outcomes were queried via a telephone interview.

Results: One hundred patients (male/female ratio 1.27) with a median age of 9.2 years (range 0.7-17.2) at symptoms onset were evaluated. The median follow-up was 2.5 years (range 0.2-18.1). An autologous serum skin test was positive in 46.7% of the subjects (n = 45), with a female predominance (71.4%) (p = 0.023). In 13.8% of the children, ANA titers were over 1/100. Food allergy (n = 1), thyroid autoantibodies (n = 3), possible collagen disease (n = 1), and drug usage (deferoxamine) (n = 1) were found to be associated factors. Infections could not be confirmed as the cause of CSU. Recovery was seen in 16.5, 38.8, and 50.0% of the children after 12, 36, and 60 months, respectively. Though in multivariate analysis none of the factors, including age, gender, autologous serum skin test positivity, the presence of angioedema, or other allergic diseases, appeared to predict the prognosis, in univariate analysis being female and being older than 10 years of age predicted an unfavorable prognosis.

Conclusion: The etiology of CSU in children is mainly related to an autoreactive background, as in adults. CSU has a favorable prognosis, and resolution is seen in half of the children within 5 years. Girls older than 10 years may have an unfavorable prognosis.

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Fibrocytes: emerging effector cells in chronic inflammation.


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Fibrocytes are mesenchymal cells that arise from monocyte precursors. They are present in injured organs and have both the inflammatory features of macrophages and the tissue remodelling properties of fibroblasts. Chronic inflammatory stimuli mediate the differentiation, trafficking and accumulation of these cells in fibrosing conditions associated with autoimmunity, cardiovascular disease and asthma.

This Opinion article discusses the immunological mediators controlling fibrocyte differentiation and recruitment, describes the association of fibrocytes with chronic inflammatory diseases and compares the potential roles of fibrocytes in these disorders with those of macrophages and fibroblasts.

It is hoped that this information prompts new opportunities for the study of these unique cells.

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Simplified COPD screening: validation of the PiKo-6® in primary care.


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AIMS: To determine the accuracy of the forced expiratory volume ratio at one and six seconds (FEV1/FEV6) using a hand-held, expiratory flow meter (PiKo-6®, nSpire Health, Inc.) to screen for chronic obstructive pulmonary disease (COPD) in primary care settings.

METHODS: Current and former smokers (> 50 years old) with no previous respiratory diagnosis (case finding [CF] = 204 subjects) or with an asthma diagnosis (differential diagnosis [DD] = 93 subjects) were evaluated using validated questionnaires, pre-bronchodilator (BD) FEV1/FEV6 and post-BD FEV1/forced vital capacity (FVC) spirometry.

RESULTS: The PiKo-6® FEV1/FEV6 showed good sensitivity and specificity (areas under the Receiver Operating Characteristic curves [95% confidence intervals]: CF = 0.85 [0.79, 0.90]; DD = 0.88 [0.80, 0.96]) and exceeded the accuracy of the questionnaires. An FEV1/FEV6 cutoff < 0.75 provided optimal sensitivity (CF = 81%; DD = 86%) and specificity (CF = 71%; DD = 67%) for COPD screening.

CONCLUSIONS: The PiKo-6® allows simple and reliable screening for COPD which could optimise early referral for spirometry and early, targeted interventions for COPD.

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