We thank Richard Hewitt and colleagues for their comments. Determining the best strategy and combination of tests for detection of latent tuberculosis (TB) infection (LTBI) is limited by the lack of gold standard for the diagnosis of LTBI. Increasing the number of tests may improve the sensitivity of latent TB detection, but at the cost of specificity, with an increased false-positive rate.

Between 1990 and 2010, chronic obstructive pulmonary disease (COPD) moved from the fourth to third most common cause of death worldwide.

Using data from the Global Burden of Disease programme we quantified regional changes in the number of COPD deaths and COPD mortality rates between 1990 and 2010. We estimated the proportion of the change that was attributable to gross national income per capita and an index of cumulative smoking exposure, and quantified the difference in mortality rates attributable to demographic changes.

Despite a substantial decrease in COPD mortality rates, COPD deaths fell only slightly, from three million in 1990 to 2.8 million in 2010, because the mean age of the population increased. The number of COPD deaths in 2010 would have risen to 5.2 million if the age- and sex-specific mortality rates had remained constant. Changes in smoking led to only a small increase in age- and sex-specific mortality rates, which were strongly associated with changes in gross national income.

The increased burden of COPD mortality was mainly driven by changes in age distribution, but age- and sex-specific rates fell as incomes rose. The rapid response to increasing affluence suggests that changes in COPD mortality are not entirely explained by changes in early life.

The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) is strongly recommended by the World Health Organization as an initial diagnostic test for treatment-experienced patients of any retreatment category [1–3]. Yet, retreatment tuberculosis (TB) suspects have been infrequently included in studies of Xpert [4], probably because current-generation PCR-based tests are unable to determine Mycobacterium tuberculosis viability [5]. Indeed, Xpert is known to frequently remain positive at the end of standard short-course therapy [6], with case reports emerging of Xpert false-positivity for up to 5 years post-treatment completion [7, 8]. Furthermore, 56% (n=3485/6285) of specificity data informing the most recent Cochrane meta-analysis [4] was derived from validation and demonstration studies [9, 10], which may be optimistic due to selection bias related to post-enrolment exclusions [7]. Not surprisingly, there have been increasing calls to clarify the guidelines for use of Xpert among treatment-experienced patients [11].

In the quest to investigate small airway function in a range of lung diseases, multiple-breath washout tests have been applied for their potential to represent the most peripheral air spaces [1, 2]. The aim of reducing the burden on the patient has recently also revived interest in the single-breath washout. A single-breath washout test has now been proposed which involves an inhalation of 5% SF₆, 26.3% He, 21% O₂ and the balance as N₂ in order to obtain a so-called dual gas tracer (DTG) phase III slope [3]. After having been introduced as a practical and promising lung function tool [3] and as an early detection tool in cystic fibrosis lung disease [4], the DTG phase III slope is now advocated as a specific index of acinar function abnormality in children with mild asthma [5]. An editorial in the European Respiratory Journal [6], reflecting upon a DTG reproducibility study in normal subjects and chronic obstructive pulmonary disease (COPD) patients [7], rightly pointed out that the clinical utility of DTG indices will depend on their actual physiological meaning. We provide here a critical appraisal of the physiological meaning of the DTG phase III slope.