Patients with asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) have been largely excluded from pivotal therapeutic trials and, as a result, its treatment remains poorly defined and lacking firm evidence. To date, there is no universally accepted definition of ACOS, which has made it difficult to understand its epidemiology or pathophysiology. Despite many uncertainties, there is emerging agreement that some of the key features of ACOS include persistent airflow limitation in symptomatic individuals 40 years of age and older, a well-documented history of asthma in childhood or early adulthood and a significant exposure history to cigarette or biomass smoke. In this perspective, we propose a case definition of ACOS that incorporates these key features in a parsimonious algorithm that may enable clinicians to better diagnose patients with ACOS and most importantly enable researchers to design therapeutic and clinical studies to elucidate its epidemiology and pathophysiology and to ascertain its optimal management strategies.

We welcome the findings by Barcellini et al. [1] in their recent publication on the first independent evaluation of QuantiFERON-TB Plus (QFT-Plus; QIAGEN GmbH, Hilden, Germany). The authors conclude that the addition of novel peptides, aimed at stimulating a CD8⁺ T-cell response, resulted in a diagnostic sensitivity for culture-confirmed tuberculosis of 88% suggesting that the QFT-Plus might offer improved sensitivity when compared with the most recent meta-analysis for QuantiFERON-TB Gold In-Tube (QFT-GIT) [2]. The findings also reinforce recent evidence supporting the theory that CD8⁺ T-cells have a major role in host defence by stimulating the production of interferon- and other soluble factors, activating macrophages which in turn suppress the growth of Mycobacterium tuberculosis (MTB) [3]. We agree with the statement of Barcellini et al. [1] on the need to corroborate such findings and assess sensitivity in CD4⁺ T-cell depleted patient populations, as in HIV-infected patients where it has been shown that CD8⁺ T-cells associate with active tuberculosis (TB) [4].

Community-acquired pneumonia (CAP) remains amongst the most common causes of infectious disease-related death worldwide. However, despite its clinical importance the existing routine microbiology tests for CAP pathogens have significant limitations, lacking sensitivity for identifying the causative pathogen and only altering management in a minority of patients. For example, blood cultures identify a pathogen in ≤10% of CAP cases [1, 2] and results are usually only available after 24 h. Therefore, clinicians are still required to prescribe broad-spectrum antibiotics for the first 24–72 h, which is the period of highest risk for clinical deterioration and death [3, 4]; even when bacteria are cultured this only rarely leads to a change in treatment and may miss co-infection [2, 5]. These limitations have led to suggestions that patients admitted with CAP do not require routine microbiological testing with management decisions based solely on clinical factors. However, not identifying the causative pathogens in CAP has important implications. From a public health perspective, not performing microbiological testing could result in failure to identify important changes in microbial aetiology or changes in anti-microbial resistance patterns. In the absence of microbiological testing all patients would be treated with prolonged broad-spectrum antibiotics that may not be required if, for example, Streptococcus pneumoniae was the causative pathogen, thereby unnecessarily increasing drug cost and potentially promoting the development of antimicrobial resistance or anti-microbial-related complications such as Clostridium difficile diarrhoea [6]. Finally, the relatively rare CAP patient infected with a drug-resistant pathogen, such as community-acquired methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa, may not be identified, thus increasing the chance of a poor outcome.

While the role of the adrenergic nervous system in the progression of left ventricular failure has been well established, its contribution to the pathogenesis of pulmonary arterial hypertension (PAH) and the resultant right ventricular failure is far less clear. The earliest attempts to treat PAH included drugs that were α-adrenergic agonists such as tolazoline [1] and isoproterenol [2]; unfortunately, their administration usually resulted in systemic hypotension and little evidence of a beneficial effect on pulmonary circulatory or right ventricular dynamics. More recently, interest has shifted towards targeting the β-adrenergic pathway as a therapeutic strategy for PAH. Nebivolol, a β₁ antagonist and β_2–3 agonist, inhibits proliferation of pulmonary vascular cells and produces endothelial and nitric oxide-dependent relaxation of pulmonary artery rings [3]; both nebivolol and pulmonary artery sympathetic denervation (PADN) attenuate vascular remodelling in monocrotaline-treated rats [3, 4], and single-centre preliminary results of PADN in PAH patients are of considerable interest [5]. In this issue of the European Respiratory Journal, van Campen et al. [6] report the results of their single-centre study of the effects of β-adrenergic blockade in patients with PAH. Their results reinforce the notion that the pulmonary and systemic circulations and their respective ventricles behave very differently both in the pathogenesis of disease states and in response to targeted therapies.