It is increasingly recognized that both asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with a large inter-individual variability with respect to their clinical expression, disease progression, and responsiveness to the available treatments.

The introduction of asthma-COPD overlap syndrome (ACOS) may lead to a better clinical characterization and improved treatment of patients with obstructive airways disease. However, it is still in its early phase and several improvements will have to be made. First, a clear definition of ACOS and preferably also its sub-phenotypes, eg, asthma-ACOS and COPD-ACOS, is urgently needed. That would also allow researchers to design clinical studies in well-defined patients. The latter is important since the interpretation of clinical studies performed so far is hampered by the use of many different definitions of ACOS. Second, future studies are needed to investigate the role of state-of-the-art techniques such as computed tomography, genetics, and genomics in the phenotyping of patients with obstructive airways disease, ie, asthma, COPD, and ACOS. Third, longitudinal studies are now needed to better define the clinical implications of ACOS with respect to the long-term outcome and treatment of ACOS and its sub-phenotypes compared to only asthma or COPD.

Xpert MTB/RIF Results in Patients With Previous Tuberculosis: Can We Distinguish True From False Positive Results?

Clin Infect Dis. 2016 Feb 16;

Authors: Theron G, Venter R, Calligaro G, Smith L, Limberis J, Meldau R, Chanda D, Esmail A, Peter J, Dheda K

Abstract
BACKGROUND:  Patients with previous tuberculosis may have residual DNA in sputum that confounds nucleic acid amplification tests such as Xpert MTB/RIF. Little is known about the frequency of Xpert-positive, culture-negative ("false positive") results in retreatment patients, whether these are distinguishable from true positives, and whether Xpert's automated filter-based wash step reduces false positivity by removing residual DNA associated with nonintact cells.
METHODS:  Pretreatment patients (n = 2889) with symptoms of tuberculosis from Cape Town, South Africa, underwent a sputum-based liquid culture and Xpert. We also compared Xpert results from dilutions of intact or heat-lysed and mechanically lysed bacilli.
RESULTS:  Retreatment cases were more likely to be Xpert false-positive (45/321 Xpert-positive retreatment cases were false-positive) than new cases (40/461) (14% [95% confidence interval {CI}, 10%-18%] vs 8% [95% CI, 6%-12%]; P = .018). Fewer years since treatment completion (adjusted odds ratio [aOR], 0.85 [95% CI, .73-.99]), less mycobacterial DNA (aOR, 1.14 [95% CI, 1.03-1.27] per cycle threshold [CT]), and a chest radiograph not suggestive of active tuberculosis (aOR, 0.22 [95% CI, .06-.82]) were associated with false positivity. CT had suboptimal accuracy for false positivity: 46% of Xpert-positives with CT > 30 would be false positive, although 70% of false positives would be missed. CT's predictive ability (area under the curve, 0.83 [95% CI, .76-.90]) was not improved by additional variables. Xpert detected nonviable, nonintact bacilli without a change in CT vs controls.
CONCLUSIONS:  One in 7 Xpert-positive retreatment patients were culture negative and potentially false positive. False positivity was associated with recent previous tuberculosis, high CT, and a chest radiograph not suggestive of active tuberculosis. Clinicians may consider awaiting confirmatory testing in retreatment patients with CT > 30; however, most false positives fall below this cut-point. Xpert can detect DNA from nonviable, nonintact bacilli.

PMID: 26908793 [PubMed - as supplied by publisher]

Related Articles

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.

Bull World Health Organ. 2016 Feb 1;94(2):147-52

Authors: Tupasi T, Gupta R, Danilovits M, Cirule A, Sanchez-Garavito E, Xiao H, Cabrera-Rivero JL, Vargas-Vasquez DE, Gao M, Awad M, Gentry LM, Geiter LJ, Wells CD

Abstract
PROBLEM: New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities.
APPROACH: We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues.
LOCAL SETTING: Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials.
RELEVANT CHANGES: Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services.
LESSONS LEARNT: Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.

PMID: 26908964 [PubMed - in process]

Physiological Mechanisms of Airways Hyperresponsiveness in Obese Asthma.

Am J Respir Cell Mol Biol. 2016 Feb 24;

Authors: Bates JH

Abstract
Obesity affects the incidence and severity of asthma in at least two major phenotypes; an early-onset allergic (EOA) form that is complicated by obesity, and a late-onset non-allergic (LONA) form that occurs only in the setting of obesity. Both groups exhibit airways hyperresponsiveness (AHR) to methacholine challenge, but exhibit differential effects of weight loss. Measurements of lung function in LONA obese asthmatics suggest that this group of individuals may simply be those unlucky enough to have airways that are more compliant than average, and that this leads to AHR at the reduced lung volumes caused by excess adipose tissue around the chest wall. In contrast, the frequent exacerbations in EOA obese asthmatics can potentially be explained by episodic inflammatory thickening of the airway wall synergizing with obesity-induced reductions in lung volume. These testable hypotheses are based on the strong likelihood that LONA and EOS obese asthma are distinct diseases. Both, however, may benefit from targeted therapeutic that impose elevations in lung volume.

PMID: 26909510 [PubMed - as supplied by publisher]