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Moving from the Oslerian paradigm to the post-genomic era: are asthma and COPD outdated terms?

In the majority of cases, asthma and chronic obstructive pulmonary disease (COPD) are two clearly distinct disease entities. However, in some patients there may be significant overlap between the two conditions. This constitutes an important area of concern because these patients are generally excluded from randomised controlled trials (mostly because of smoking history in the case of asthma or because of significant bronchodilator reversibility in the case of COPD). As a result, their pathobiology, prognosis and response to therapy are largely unknown. This may lead to suboptimal management and can limit the development of more personalised therapeutic options. Emerging genetic and molecular information coupled with new bioinformatics capabilities provide novel information that can pave the way towards a new taxonomy of airway diseases.

In this paper we question the current value of the terms ‘asthma’ and ‘COPD’ as still useful diagnostic labels; discuss the scientific and clinical progress made over the past few years towards unravelling the complexity of airway diseases, from the definition of clinical phenotypes and endotypes to a better understanding of cellular and molecular networks as key pathogenic elements of human diseases (so-called systems medicine); and summarise a number of ongoing studies with the potential to move the field towards a new taxonomy of airways diseases and, hopefully, a more personalised approach to medicine, in which the focus will shift from the current goal of treating diseases as best as possible to the so-called P4 medicine, a new type of medicine that is predictive, preventive, personalised and participatory.

The circadian clock and asthma

It is characteristic of asthma that symptoms worsen overnight, particularly in the early hours of the morning. Nocturnal symptoms in asthma are common and are an important indicator for escalation of treatment. An extensive body of research has demonstrated that nocturnal symptoms of cough and dyspnea are accompanied by circadian variations in airway inflammation and physiologic variables, including airflow limitation and airways hyper-responsiveness. The molecular apparatus that underpins circadian variations, controlled by so called ‘clock’ genes, has recently been characterised. Clock genes control circadian rhythms both centrally, in the suprachiasmatic nucleus of the brain and peripherally, within every organ of the body.

Here, we will discuss how clock genes regulate circadian rhythms. We will focus particularly on the peripheral lung clock and the peripheral immune clock and discuss how these might relate to both the pathogenesis and treatment of asthma.

Obesity hypoventilation syndrome: does the current definition need revisiting?

Obesity hypoventilation syndrome (OHS) has been conventionally (and to some extent arbitrarily) defined by the combination of obesity (body mass index (BMI) >30 kg/m2), daytime hypercapnia (arterial partial pressure of carbon dioxide (PaCO2) ≥45 mm Hg or 6 kPa) during wakefulness, and usually (but not always) the presence of ‘sleep disordered breathing’, such as obstructive sleep apnoea, rapid eye movement sleep hypoventilation or both.1 The survival curve for untreated OHS is significantly reduced compared with the non-obese,2 and so early identification and treatment for these patients is likely to be beneficial. Little is currently known about the true prevalence of OHS in ambulatory obese individuals, with estimates range from 0.3–0.4% of the general population,3 to around 30% of hospitalised patients with a BMI >35 kg/m2.2 The combined medical costs associated with treatment of obesity associated diseases are estimated to increase by $48–66 billion/year in the...

The hazards of smoking in women: results from the Million Women Study

Smoking is associated with many diseases and remains a major cause of mortality. The Million Women Study is a large UK prospective cohort study of women born in the second quarter of the 20th century, collecting data for a broad range of health issues. Women were recruited and sent questionnaires that included lifestyle factors such as smoking at baseline, 3 years and 8 years. After excluding women with previous smoking-associated diseases, 1.2 million invited participants were followed up for mortality for a mean of 12 years via national mortality records.

Current smokers had a threefold increase in mortality compared with never-smokers, with adjusted mortality rate ratio increasing almost linearly with the number of cigarettes smoked at baseline. Relative risks were highest for deaths due to chronic lung disease and lung cancer. Ex-smokers had lower but still raised relative risks. Applying their results to a hypothetical population, the authors calculated that smokers lose...

Against all odds: anti-IgE for intrinsic asthma?

For many years, pathogenetic concepts and the results of clinical trials supported the view that anti-IgE treatment is specifically effective in allergic asthma. However, there is now growing clinical and mechanistic evidence suggesting that treatment with the anti-IgE antibody omalizumab can be effective in patients with intrinsic asthma. Therefore, large and well-controlled clinical trials with anti-IgE are urgently warranted in patients with intrinsic asthma.

In addition, there is a need to find new biomarkers which can identify patients with asthma who respond to anti-IgE treatment.

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