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Asthma research in focus

Air pollution exposure during pregnancy linked with asthma risk

Babies born to mothers exposed to air pollution from traffic sources during pregnancy have an increased risk of developing asthma before the age of five years of age, according to a new study.

The study, which was published in the European Respiratory Journal last month, found that exposure to air pollution from traffic sources was linked to an increased risk of developing asthma even in urban areas with relatively low levels of pollution.

Children whose mothers lived close to highways during pregnancy had a 25 per cent increased relative risk of developing asthma before the age of five.

The risk increased with an increase in levels of nitrogen dioxide and carbon monoxide, which are two markers of traffic-related air pollution. In addition, children born with a low birth weight were more susceptible to the respiratory effects of air pollution. The results were found after other factors, such as low birth weight at term, gestational period, breastfeeding and socio-economic factors had been controlled for.

The new research is one of the largest studies to look at the role of variation in air pollution in urban areas and the development of asthma.

Over 65,000 Canadian children were included in the study and followed up from birth until the age of 10 years. The researchers monitored physician-diagnosed asthma cases among this group and also assessed exposure of the mothers to air pollutants during pregnancy. Each mother’s postcode was used and exposure level was determined using three measures. These were: Land use regression models, which combine traffic-related air pollutant monitoring data and geographical information around the home address; measurements of air pollutants from monitoring stations close to each mother; and assessing whether each mother in the study lived close to a major road.

The measurements focused mainly on traffic-related pollutants, including black carbon, fine particulate matter, nitrogen oxide and nitric oxide.

Lead author, Dr Hind Sbihi, from the University of British Columbia, Vancouver, said: “Our study results highlight the importance of exposure to pollution while babies are still in the womb. Air pollution from traffic sources increased the risk of developing asthma during early years before children reach school age, even in an urban area with relatively low levels of air pollution. There are some measures individuals can take to reduce this risk. First we would suggest installing high-efficiency particulate air (HEPA) filters in the home and avoiding busy routes when taking a stroll. You can also check air quality levels online and postpone high-intensity physical activity until conditions improve.”

Speaking about the findings, Chair of the European Lung Foundation, Mr Dan Smyth, said: “Air pollution affects 100 per cent of the population and this study highlights the harmful effects of air pollution right from the moment we are created. A large proportion of Europe’s population live in areas with unhealthy outdoor air and it is essential that we increase awareness of the dangers of polluted air. Our Healthy Lungs for Life campaign aims to do this by focusing on measures to help prevent damaging lung conditions. Urgent action is needed to tackle the rising levels of air pollution. We believe that an ambitious EU National Emission Ceilings (NEC) Directive, which revises limit values for ambient air and which is currently negotiated between the EU institutions, is an essential tool to achieve this aim.”

Asthma over-diagnosed in primary care, study finds

Over diagnosis of childhood asthma is common in primary care, leading to unnecessary treatment, disease burden, and impact on quality of life, according to new research.

The study, published in the British Journal of General Practice, aimed to assess the extent and characteristics of confirmed and unconfirmed diagnoses of asthma in children who were diagnosed by their GP as having asthma or who were treated as having asthma.

For the study, a retrospective analysis in four academic primary healthcare centres in Utrecht, the Netherlands, was conducted.

Routine care registration data of children aged six–18 years who received a diagnosis of asthma or were treated as having asthma were analysed.

The analysis found in only 16.1 per cent of the children diagnosed with asthma was the diagnosis confirmed with spirometry, whereas in 23.2 per cent the signs and symptoms did give rise to suspected asthma but the children should have undergone further lung function tests.

In more one-half (53.5 per cent) of the children the signs and symptoms made asthma unlikely and thus they were most likely over-diagnosed.

The remaining 7.2 per cent were probably correctly classified as not having asthma.

The main reasons for classifying asthma without children undergoing further lung function tests were dyspnoea (31.9 per cent), cough (26 per cent), and wheezing (10.4 per cent).

In addition to finding that over-diagnosis of childhood asthma is common in primary care, leading to unnecessary treatment, disease burden, and impact on quality of life, the authors stated that only a small percentage of children have a diagnosis of asthma confirmed by lung function tests.

Yale study identifies new target for severe asthma and chronic inflammation

A new Yale University-led study has identified a protein from platelets — Dkk-1 — that contributes to chronic inflammation and has also revealed the role of platelets in the immune response.

The research, published in the February issue of the journal Immunity, could lead to the development of new therapies to treat severe asthma and other inflammatory diseases, say the researchers.

Chronic inflammation is commonly found in asthma, autoimmune diseases, cancer, and viral infections, and is characterised by constant activation of platelets with unhealed tissue damage.

To investigate the role of Dkk-1 in various inflammatory diseases, Yale Professor of Immunobiology Dr Alfred Bothwell and his co-authors studied the effect of the common house-dust mite and a parasite on normal mice and those lacking Dkk-1.

They found that by blocking Dkk-1 genetically or pharmacologically, the animals were protected from asthma and parasitic infection.

The results demonstrated a functional and physical link between platelets and lymphocytes via Dkk-1.

“Remarkably, without the presence of Dkk-1, both innate and adaptive immune responses for chronic inflammation could not be triggered,” said Dr Wook-Jin Chae, Yale Associate Research Scientist in Immunobiology and first author.

“Because Dkk-1 is from platelets and it inhibits tissue repair, now we know how platelets become an essential part of the immune response and tissue repair simultaneously in response to inflammation.”

With this new finding, Drs Bothwell and Chae established a new target for treating inflammatory diseases.

“The potential in other chronic diseases such as cancer and autoimmunity is enormous,” said Dr Bothwell. The next step is to harness Dkk-1 in cancer immunotherapy.

“We are looking for small molecule compounds that could block Dkk-1-mediated signalling in the inflamed tissue,” the authors said.

Link between asthma and fertility posited

A new study has found that women with asthma may find it takes them longer to become pregnant.

The authors of the study, which was published in the European Respiratory Journal, stated that evidence is increasing of an association between asthma and aspects of female reproduction. However, current knowledge is limited and furthermore relies on questionnaire studies or small populations.

The prospective observational cohort study aimed to investigate whether time to pregnancy, the number of fertility treatments, and the number of successful pregnancies differ significantly in women with unexplained infertility with and without asthma.

A total of 245 women with unexplained infertility (aged 23-45 years) underwent questionnaires and asthma and allergy testing while undergoing fertility treatment. Some 96 women entering the study had either a former doctor’s diagnosis of asthma or were diagnosed with asthma when included. After inclusion they were followed for a minimum of 12 months in fertility treatment, until they had a successful pregnancy, stopped treatment, or the observation ended.

The likelihood of achieving pregnancy was lower in women with asthma compared with those without asthma: median total time to pregnancy was 32.3 months in non-asthmatic women versus 55.6 months in those with asthma.

Women with asthma had fewer successful pregnancies during fertility treatment, 39.6 per cent versus 60.4 per cent. Increasing age was of negative importance for expected time to pregnancy, especially among asthmatic women

“Female asthmatics had a longer time to pregnancy and less often became pregnant than non-asthmatic women,” according to the authors.

“Increasing age reduced the chances of conceiving especially among asthmatic women.”

However the authors acknowledged that the causal relationship between asthma and subfertility remains unclear.

Prothrombotic state in patients with severe and prednisolone-dependent asthma

People with severe asthma have an increased risk of pulmonary embolism, a new study has found.

The study, which was published in the Journal of Allergy and Clinical Immunology, sought to determine if, therefore, severe asthmatics are prothrombotic by comparing coagulation and fibrinolysis between healthy subjects and those with asthma.

The investigators enrolled 126 adults (33 control, 31 mild asthma, 32 severe asthma, 30 steroid dependent asthma) for blood draw.

Endogenous thrombin potential (ETP), plasmin-α2-antiplasmin complex, plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF) were increased in asthmatics compared to controls.

The authors observed increased ETP (121 per cent vs 99 per cent, overall P < .01), plasmin-α2-antiplasmin complex (520 vs 409 µg/L, overall P = .04), PAI-1 (10 vs 7 ng/mL, overall P = .02), and vWF (142 per cent vs 87 per cent, overall P < .01) levels in asthmatic patients compared with healthy control subjects.

The findings showed ETP, PAI-1, and vWF levels increased with increasing asthma severity.

In addition, the study found a correlation between ETP and vWF with neutrophil but not eosinophil counts.

“Asthmatic patients have a prothrombotic state that increases with asthma severity,” according to the authors.

“This might explain why patients with asthma, in particular those with severe disease, have an increased risk of venous thromboembolism.”

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