FeNO measurement an effective asthma screening tool in young adults 
Apr 10, 2008 - MedWire News: Measuring the fraction of exhaled nitric oxide (FeNO) in young adults using a portable analyzer is an effective means of screening for asthma, according to Greek research.

However, the authors of the study caution in the journal Chest that allergic rhinitis and current smoking are significant confounding factors.

FeNO has previously been studied as a screening tool for asthma in children, but until now has not been evaluated in an adult population.

Konstantinos Kostikas and colleagues from the University Hospital of Larissa measured the FeNO values during pollen season of 149 university students with at least one respiratory symptom of asthma and 70 symptom-free controls, using a portable analyzer.

Each student also underwent spirometry testing and was evaluated by a physician blinded to FeNO measurements to determine an asthma diagnosis.

A total of 63 students were diagnosed with asthma, while 57 were diagnosed with allergic rhinitis. Asthmatics exhibited higher FeNO values than controls (20 parts per billion [ppb] vs 11 ppb), but did not differ significantly from students with allergic rhinitis (17 ppb).

FeNO values >19 ppb had 85.2% specificity and 52.4% sensitivity for the diagnosis of asthma (area under the curve [AUC]=0.723) across all students, but stratification according to smoking status showed that diagnostic performance was better for nonsmokers (AUC=0.805). However, a FeNO value >25 ppb had specificity >90% for the diagnosis of asthma in both smokers and nonsmokers.

“We report that FeNO measured by a portable analyzer may be used as a screening tool for asthma in a steroid-naive population of young adults during pollen season,” the authors write.

They conclude: “In the era of wider availability and lowering cost of FeNO analyzers, further studies in other age groups are warranted for its validation as a screening tool for asthma in the general population.”

Chest 2008; 133, 906-913

Curry constituent might benefit allergy sufferers 
Apr 11, 2008 - MedWire News: Curcumin, which adds the yellow color to curry, inhibits Syk kinase-dependant signalling events in mast cells and shows antiallergic activity in a mast-cell–dependent model of allergy, researchers report.

Writing in the Journal of Allergy and Clinical Immunology, the authors suggest that curcumin might be useful for the treatment of mast-cell–related immediate and delayed allergic diseases such as allergic rhinitis and asthma.

Mast cells are known to be associated with various allergic and autoimmune disorders, and tyrosine kinases such as Syk have been touted as potential therapeutic targets for suppression of mast-cell activation.

Wahn Soo Choi (Konkuk University, Korea) and colleagues investigated the antiallergic and potential Syk-inhibitory activity of curcumin in mast-cell cultures and a passive cutaneous anaphylaxis mouse model.

They found that curcumin inhibited the antigen-mediated activation of
mast cells and passive cutaneous anaphylaxis in mice.

Concentrations as low as 3 µmol/l of curcumin suppressed degranulation and the secretion of tumor necrosis factor TNF-a and interleukin-4 in activated mast cells. Similar concentrations suppressed the Syk-dependent phosphorylations of the adaptor proteins linker of activated T-cells and Grb2-associated binder 2, which are crucial for mast cell activation.

Curcumin directly inhibited Syk kinase activity in vitro, and also inhibited activating phosphorylations of Akt and the mitogen-activated protein kinases p38, p44/42 (extracellular signal-regulated kinase 1/2), and c-Jun N-terminal kinase, which are crucial for the production of inflammatory cytokines.

“Curcumin possesses antiallergic activity in a mast-cell-dependent model, most likely through its ability to potently inhibit Syk-mediated signals,” the authors write.

Syk inhibition has been shown to reduce allergic airway inflammation, and syk inhibitors are also being evaluated for use in nasal sprays for the treatment of symptoms of seasonal allergic rhinitis, the authors explain. They suggest that curcumin has similar potential for topical therapy of various allergic diseases, including allergic rhinitis, especially in view of its low toxicity in human subjects.

Choi and colleagues conclude: “Further evaluation of its [curcumin] utility in the treatment of immediate and delayed allergic diseases is warranted”

J Allergy Clin Immunol 2008; Advance online publication

High starting dose of ICS better for patients with established asthma
Apr 09, 2008 - MedWire News: Patients with newly diagnosed asthma respond well to treatment with inhaled corticosteroids (ICS) irrespective of the starting dose, but patients with established asthma respond significantly better to a higher starting dose, according to Olaf Selroos from Mjölbolsta Hospital in Karis, Finland.

There is no consensus at present on whether treatment with ICS in asthma should be initiated with a high or low dose, and the Global Initiative for Asthma guidelines offer no advice on the subject.

Selroos designed a placebo-controlled, double-blind, parallel-group study to investigate the importance of disease duration on the response to the starting dose of ICS in asthma patients not previously treated with ICS.

Forty patients with newly diagnosed asthma (symptoms for <12 months) and 41 patients with established asthma (mean duration of 5.2 years) were randomly assigned to receive treatment with either 100 or 400 µg budesonide turbuhaler or placebo, twice daily for 12 weeks.

After 12 weeks all four ICS treatments resulted in statistically significant improvements in morning peak expiratory flow (mPEF) from baseline relative to placebo.

There was no significant difference between the responses to different ICS doses in patients with newly detected asthma.

By contrast, patients with established symptoms responded significantly better to a dose of 800 µg/day compared with patients who received 200 µg/day. In addition, the 800 µg/day dose in the early treatment group improved mPEF significantly more than in the delayed treatment group.

“It appears possible to conclude based on these study results that starting with a higher dose of budesonide may be clinically important in adult patients with a longer duration of asthma,” Selroos writes.

He concludes: “In patients with a duration of asthma symptoms <12 months the choice of starting dose does not seem to matter.”

Respir Med 2008; Advance online publication

 
Cigarette smoke exposure impairs lung homeostasis in infant lungs
Apr 04, 2008 - MedWire News: Exposure to cigarette smoke inhibits innate gene expression and impairs alveolar growth in neonatal mice, US researchers report.

Writing in the American Journal of Respiratory Cell and Molecular Biology, Sharon McGrath-Morrow from The Johns Hopkins Medical Institutes, Baltimore, suggest that their findings “may in part explain the increased incidence of respiratory symptoms in infants and children exposed to cigarette smoke.”

Infants exposed to cigarette smoke are at higher risk for sudden infant death syndrome, lower respiratory tract infections, and small airway disease, compared with infants not exposed to cigarette smoke, suggesting that perinatal life represents a period of vulnerability during which exposure to cigarette smoke may impair lung immunity and lung growth.

To investigate the effects of cigarette smoke exposure on the neonatal lung, McGrath-Morrow and team exposed neonatal mice to cigarette smoke for the first 2 weeks of life.

Pulmonary gene-expression profiling revealed that cigarette exposure significantly inhibited type 1 and type 2 interferon pathway genes in neonatal lungs, compared with age-matched control lungs.

In addition, lung volumes at 8 weeks of age were modestly but significantly decreased in mice exposed to cigarette smoke in the neonatal period compared with age-matched controls.

“We found that perinatal lung is susceptible to the effects of cigarette smoke exposure,” the authors note, adding that “in neonatal mice, daily exposure to cigarette smoke for the first 2 weeks of life inhibited the expression of many genes in the lung that are relevant to the innate immune response.”

The team concludes: “Our murine model of cigarette smoke-induced neonatal lung injury may be useful in investigating pathways that are disrupted or altered in developing lung exposed to cigarette smoke, and may help with understanding the overall detrimental effects of smoke exposure on the developing lung.”

Am J Respir Cell Mol Biol 2008; 38: 393-400

 
High BMI in young adults linked to increased lung decline later in life 
Apr 08, 2008 - MedWire News: Healthy young adults with a low body mass index (BMI) score are able to maintain lung function until well into their fourth decade of life, whereas young adults with a high BMI experience a pronounced 10-year decline in lung function, according to results published in the journal Respiratory Research.

“These results suggest that the obesity epidemic threatens the lung health of the general population,” explain David Jacobs (University of Minnesota, Minneapolis, USA) and colleagues.

Recent research has shown that the prevalence of obesity has increased in the US from 10.9% in 1996 to 22.1% in 2001 in young adults aged 19-26 years, but the association between BMI and future lung function in young adulthood is unclear.

Jacobs and team used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to quantify age-related changes in forced vital capacity (FVC), FEV1, and FEV1/FVC ratio according to baseline BMI and BMI changes.

The team estimated 10-year change in FVC, FEV1 and FEV1/FVC according to baseline BMI and change in BMI within birth cohorts with initial average ages 20, 24, and 28 years in a large cohort of 5,115 Black and White men and women, aged 18-30 years.

Adults with a baseline BMI <21.3 kg/m2 experienced 10-year increases of 71 ml in FVC and 60 ml in FEV1, with neither measure declining up to 38 years.
By contrast, participants with a baseline BMI >26.4 kg/m2 experienced 10-year decreases of 185 ml in FVC and 64 ml in FEV1.

In addition, those who gained the most weight over 10 years had the largest decrease in FVC, but FVC increased with weight gain in those initially thinnest. However, FEV1 decreased with increasing weight gain in all participants, with maximum decline in obese individuals who gained the most weight during the study.

“Loss of lung function by age 38 was not inevitable in these healthy young adults, although those with highest BMI suffered substantial losses,” the authors write.

They conclude: “Whatever the predominant mechanism(s) responsible for these changes might be, these data indicate that maximal lung function may be maintained well into the fourth decade of life; and that, in addition to its other effects on health and disease, the obesity epidemic may threaten the lung function and as a consequence the lung health of the general population.”

Respir Res 2008; 9: 31