B. Ronan O'Driscoll

Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study.

RATIONALE Some patients with severe asthma are immunologically sensitized to one or more fungi, a clinical entity categorized as severe asthma with fungal sensitization (SAFS). It is not known whether SAFS responds to antifungal therapy. OBJECTIVES To evaluate the response of SAFS to oral itraconazole. METHODS Patients with severe asthma sensitized to at least one of seven fungi by skin prick or specific IgE testing were recruited. All had total IgE less than 1,000 IU/ml and negative Aspergillus precipitins. They were treated with oral itraconazole (200 mg twice daily) or placebo for 32 weeks, with follow-up for 16 weeks. MEASUREMENTS AND MAIN RESULTS The primary end point was change in the Asthma Quality of Life Questionnaire (AQLQ) score, with rhinitis score, total IgE, and respiratory function as secondary end points. Fifty-eight patients were enrolled, of whom 41% had been hospitalized in the previous year. Baseline mean AQLQ score was 4.13 (range, 1-7). At 32 weeks, the improvement (95% confidence interval) in AQLQ score was +0.85 (0.28, 1.41) in the antifungal group, compared with a -0.01 (-0.43, 0.42) change in the placebo group (P = 0.014). Rhinitis score improved (-0.43) in the antifungal, and deteriorated (+0.17) in the placebo group (P = 0.013). Morning peak flow improved (20.8 L/minute, P = 0.028) in the antifungal group. Total serum IgE decreased in the antifungal group (-51 IU/ml) but increased in placebo group (+30 IU/ml) (P = 0.001). No severe adverse events were observed, but seven patients developed adverse events requiring discontinuation, five in the antifungal group. CONCLUSIONS SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients.

Active Lung Fibrosis up to 17 Years after Chemotherapy with Carmustine (BCNU) in Childhood

BACKGROUND Carmustine (BCNU) is an anticancer drug known to produce pulmonary fibrosis as a side effect within three years of treatment. It is not known whether pulmonary fibrosis can appear later. METHODS To investigate the clinical range of this side effect, we studied the survivors among 31 children treated with carmustine for brain tumors between 1972 and 1976. Fourteen had died of their tumor; of the remaining 17, 6 had died of lung fibrosis--2 within 3 years of treatment and 4 from 8 to 13 years after treatment. This report focuses primarily on the 11 survivors, 8 of whom were available for detailed study 13 to 17 years (mean, 14) after treatment. RESULTS Of the eight survivors studied, six had abnormal chest radiographs showing predominantly upper-zone fibrotic changes. These patients also had abnormal CT scans, showing a previously undescribed pattern of upper-zone fibrosis. All the survivors studied had restrictive spirometric defects (mean [+/- SD] vital capacity, 54 +/- 19 percent of the predicted value). Bronchoalveolar-lavage fluid contained abnormal proportions of specific macrophage subgroups. Light and electron microscopy in six patients revealed interstitial fibrosis and elastosis with damage to epithelial and endothelial cells. Four patients had symptoms (shortness of breath, cough, or both). CONCLUSIONS Carmustine chemotherapy in childhood causes lung fibrosis that may remain asymptomatic for many years or become symptomatic at any time.

Mold sensitization is common amongst patients with severe asthma requiring multiple hospital admissions

BackgroundMultiple studies have linked fungal exposure to asthma, but the link to severe asthma is controversial. We studied the relationship between asthma severity and immediate type hypersensitivity to mold (fungal) and non-mold allergens in 181 asthmatic subjects.MethodsWe recruited asthma patients aged 16 to 60 years at a University hospital and a nearby General Practice. Patients were categorized according to the lifetime number of hospital admissions for asthma (82 never admitted, 53 one admission, 46 multiple admissions). All subjects had allergy skin prick tests performed for 5 mold allergens (Aspergillus, Alternaria, Cladosporium, Penicillium and Candida) and 4 other common inhalant allergens (D. pteronyssinus, Grass Pollen, Cat and Dog).ResultsSkin reactivity to all allergens was commonest in the group with multiple admissions. This trend was strongest for mold allergens and dog allergen and weakest for D. pteronyssinus. 76% of patients with multiple admissions had at least one positive mold skin test compared with 16%-19% of other asthma patients; (Chi squared p < 0.0001). Multiple mold reactions were also much commoner in the group with multiple admissions (50% V 5% and 6%; p < 0.0001). The number of asthma admissions was related to the number and size of positive mold skin allergy tests (Spearman Correlation Coefficient r = 0.60, p < 0.0001) and less strongly correlated to the number and size of non-mold allergy tests (r = 0.34, p = 0.0005). Hospital admissions for asthma patients aged 16–40 were commonest during the mold spore season (July to October) whereas admissions of patients aged above 40 peaked in November-February (Chi Squared, p < 0.02).ConclusionThese findings support previous suggestions that mold sensitization may be associated with severe asthma attacks requiring hospital admission.

NEBULISED SALBUTAMOL WITH AND WITHOUT IPRATROPIUM BROMIDE IN ACUTE AIRFLOW OBSTRUCTION

103 patients with acute airflow obstruction (56 asthma, 47 chronic obstructive pulmonary disease [COPD]) completed a double-blind trial of nebulised bronchodilator treatment in a hospital accident and emergency department. Each patient was randomised to receive either 10 mg of salbutamol nebuliser solution in 2 ml of saline or 10 mg of salbutamol in 2 ml (0.5 mg) of preservative-free ipratropium bromide. Peak flow rate (PFR) was recorded before treatment and 1 hour after beginning nebulised treatment. In 23 asthmatic patients given salbutamol alone PFR rose by a mean 31% 1 hour after treatment whereas in 33 such patients given combined treatment it rose by a mean 77% (95% confidence interval for the difference 8-84%). Patients whose PFR was below 140 l/min at entry gained maximum benefit from the combined treatment. For COPD patients the PFR rise was almost identical for both treatments. In acute asthma the immediate PFR response to a mixture of salbutamol and ipratropium bromide was better than the response to nebulised salbutamol alone. For COPD patients, the two treatments were of equal benefit.

Survey of major complications of intercostal chest drain insertion in the UK

Background Following reports from the National Patient Safety Agency of deaths and serious harm from intercostal chest drains (ICD) we conducted a national survey among chest physicians of their experience of harm associated with ICD. Methods A questionnaire was sent to 198 UK chest physicians at 148 acute hospital trusts, enquiring about current practice and any adverse incidents related to chest drains from 2003 to 2008. Results 101 of 148 trusts (68%) replied. 67 trusts reported at least one major incident involving ICD insertion. 31 Cases of ICD misplacement were reported with seven deaths. Misplaced drains were inserted in liver (10), peritoneal space (6), heart (5), spleen (5), subclavian vessels (2), colon (1), oesophagus (1) and inferior vena cava (1). 47 cases of serious lung or chest wall injuries with eight deaths and six cases of ICD placement on the wrong side with two deaths were reported. The guidewire was lost in the pleural cavity in three cases. 22 of 101 trusts required written patient consent before ICD insertion. 11 trusts had a training policy. 16 trusts had patient information literature for this procedure. The seniority of doctors permitted to insert ICDs was as follows: 30% any doctor; 27% at least 1 year post qualification; 32% at least 2 years, 11% at least 4 years. Conclusions 67% of responding trusts had encountered major complications of ICD. The survey raised concerns about training and consent. The National Patient Safety Agency has made recommendations to address these risks which are also addressed in the 2009 update of the British Thoracic Society Pleural Disease Guideline.

Acute pulmonary aspergillosis in immunocompetent subjects after exposure to bark chippings

We describe 2 cases of immunocompetent males with acute community-acquired invasive pulmonary aspergillosis developing shortly after spreading bark chippings. One patient with a fatal outcome was initially diagnosed as allergic alveolitis rather than infection and received steroid treatment illustrating the obvious challenges in the differential diagnosis between these disease entities.

Effects of equipment and technique on peak flow measurements

BackgroundDifferent lung function equipment and different respiratory manoeuvres may produce different Peak Expiratory Flow (PEF) results. Although the PEF is the most common lung function test, there have been few studies of these effects and no previous study has evaluated both factors in a single group of patients.MethodsWe studied 36 subjects (PEF range 80–570 l/min). All patients recorded PEF measurements using a short rapid expiration following maximal inspiration (PEF technique) or a forced maximal expiration to residual volume (FVC technique). Measurements were made using a Wrights peak flow meter, a turbine spirometer and a Fleisch pneumotachograph spirometer.ResultsThe mean PEF was 8.7% higher when the PEF technique was used (compared with FVC technique, p < 0.0001). The mean PEF recorded with the turbine spirometer was 5.5% lower than the Wright meter reading. The Fleisch spirometer result was 19.5% lower than the Wright reading. However, adjustment of the Wrights measurements from the traditional Wrights scale to the new EU Peak Flow scale produced results that were only 7.2% higher than the Fleisch pneumotachograph measurements.ConclusionPeak flow measurements are affected by the instruction given and by the device and Peak Flow scale used. Patient management decisions should not be based on PEF measurement made on different instruments.

British Thoracic Society Oxygen Guidelines: another clinical brick in the wall

The worlds first evidence-based guideline for emergency oxygen therapy was published by the British Thoracic Society (BTS) in 2008 and endorsed by 21 other societies and colleges.1 The key message in the guideline was very simple: clinicians were advised to avoid hypoxaemia and hyperoxaemia by prescribing a normal or near-normal target oxygen saturation of 94%–98% for most acutely unwell patients and to prescribe a lower range (usually 88%–92%) for patients at risk of hypercapnia, and to use high-concentration oxygen for some conditions such as carbon monoxide poisoning or the immediate management of critical illness. This guidance has informed worldwide clinical practice and research since 2008 and is cited by more than 500 publications. The guideline is now updated and extended with the support of 22 colleges and societies.2 Readers will want to know what is new in the 2017 update of the BTS emergency oxygen guideline, published as a supplement to this edition of Thorax .2 A concise version of the guideline is available in BMJ Open Respiratory Research.3 The evidence review methodology and grading of recommendations follows the National Institute for Health and Care Excellence accredited BTS guideline production process which is based on Scottish Intercollegiate Guidelines Network (SIGN) methodology and adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument.4 The evidence base for the guideline has been updated to August 2013 with bespoke literature searches (and extended to late 2016 for key references). The remit of the guideline is wider now than in 2008. The new guideline covers emergency …