Utility of lung density measurements in the diagnosis of emphysema.

BACKGROUND: The role of computerised tomography (CT) lung density measurements in objective quantification of emphysema is uncertain. The aim of this study was to determine normal reference values for CT lung density measurements and investigate their utility in identifying subjects with clinical emphysema. METHODS: Normal subjects (non-smokers, no respiratory disease, n=185) and subjects with clinical emphysema (post-bronchodilator FEV(1)/FVC <70%, > or =10 pack years tobacco smoking, no childhood asthma and, either D(LCO)/VA <80% predicted and/or macroscopic emphysema on CT, n=22) were identified from a random population survey. Subjects underwent CT scanning, with measurement of areas of low attenuation as a percentage of total area (RA%) for three standardised slices and two reconstruction algorithms with a density threshold of -950 HU. Reference values in normal subjects, and ability of the measurements to discriminate between the two groups were determined. RESULTS: Reference values for individual subjects showed wide confidence intervals (standard resolution scans, RA% females 0.2-3.9%, males 0.4-8.7%.) Subjects with emphysema had greater RA% values compared with normal subjects, the difference being most marked in apical slices (standard resolution algorithm, apical slice, median RA% 2.9% (95% CI 0.4-11.1%) vs. 0.1% (95% CI 0.0-0.5%), emphysema vs. normal subjects, respectively). Logistic regression analysis showed poor discriminant ability to distinguish between the groups, the most favourable cut-off yielding a sensitivity and specificity of 83.3% and 62.8%, respectively. CONCLUSIONS: CT lung density measurements cannot reliably detect the presence of emphysema in an individual. We recommend further investigation into lung density measurements before their widespread use in clinical practice.

Pilot study of the safety and effect of intranasal delipidated acid-treated Mycobacterium vaccae in adult asthma.

OBJECTIVE: There is epidemiological and experimental evidence that exposure to mycobacteria has the potential to suppress the development of atopy and/or asthma. Delipidated, deglycolipidated and arabinogalactan-depleted autoclaved Mycobacterium vaccae (delipidated acid-treated M. vaccae) has been shown to suppress allergen-induced airway eosinophilia in mice. METHODOLOGY: Thirty-seven adults with stable moderately severe asthma who were skin prick test-positive to house dust mite were randomized to receive two doses 2 weeks apart of delipidated acid-treated M. vaccae (first dose 0.4 mg and second dose 0.8 mg) or phosphate buffered saline, given as drops intranasally. Safety, tolerability and markers of asthma severity (including peak flow, FEV1, major and minor exacerbations, symptom scores and beta-agonist use), and nasal symptom scores, blood eosinophil and IgE levels were monitored for 8 weeks. RESULTS: Delipidated acid-treated M. vaccae was safe and well tolerated although there was an occasional mild local reaction. There were no statistically significant differences between the treatment group and placebo for any of the outcome variables. CONCLUSIONS: There is a requirement to elucidate the reasons why mycobacterial-based vaccines have not shown equivalent efficacy in human trials compared with animal models. The role of factors such as duration of disease, route of administration and the active component of mycobacteria need to be addressed.