The level of specialist assessment of adult asthma is influenced by patient age

SummaryBackgroundLate onset asthma is associated with more severe disease and higher morbidity than in younger asthma patients. This may in part relate to under recognition of asthma in older adults, but evidence on the impact of patient age on diagnostic assessment of asthma in a specialist setting is sparse.AimTo examine the impact of patient age on the type and proportion of diagnostic tests performed in patients undergoing specialist assessment for asthma.MethodsData from a clinical population consisting of all patients consecutively referred over a 12 months period to a specialist clinic for assessment of asthma were analysed.ResultsA total of 224 patients with asthma or suspected asthma were referred during the 12 month period; 86 adults aged <35 years, 95 aged 35–55 years and 43 aged >55 years. Symptom characteristics were similar, but adults >35 years had a lower lung function than younger adults, and were more frequently smokers. However, a regression analysis showed that older age was associated with a lower likelihood of diagnostic assessment with a reversibility test, a bronchial challenge test, or measurement of exhaled NO, independently of a known diagnosis of asthma, smoking habits and lung function at referral.ConclusionA lower level of diagnostic assessment was observed already after the age of 35 years, indicating a risk for under diagnosis of asthma at an earlier patient age than previously thought

Predicting airway hyperreactivity to mannitol using exhaled nitric oxide in an unselected sample of adolescents and young adults

SummaryIncreased levels of exhaled nitric oxide (FeNO) and airway hyperresponsiveness (AHR) to inhaled mannitol are related to allergic inflammation characterized by eosinophil infiltration and a clinical response to treatment with anti-inflammatory agents in subjects with asthma. This study determines the diagnostic accuracy of FeNO using absolute and normalized values to predict the presence of AHR to inhaled mannitol in an unselected population.Levels of FeNO and AHR to inhaled, dry-powder mannitol was measured in 180 unselected, steroid-naïve, non-smoking adolescents and young adults.The area under the curve for the receiver operating characteristics curve for FeNO to identify a positive response to mannitol was 91.9% (CI95: 87.7–96.2). The optimal cut-off was 25 ppb (185% predicted) and a sensitivity of 100% (CI95: 83.9–100.0) was achieved below 20 ppb (165% predicted).FeNO is a sensitive and specific tool for predicting the response to inhaled mannitol in an unselected sample of non-smoking, steroid-naïve subjects, and a low FeNO indicates that extra diagnostic work-up using inhaled mannitol will add very little extra information

IL-33 is related to innate immune activation and sensitization to HDM in mild steroid-free asthma.

IL-33 represents a potential link between the airway epithelium and induction of a TH 2 type inflammatory response in asthma. However, the association with markers of eosinophilic airway inflammation has not previously been reported in steroid-free asthma patients

Genetic factors explain half of all variance in serum eosinophil cationic protein

Background: Eosinophil cationic protein (ECP) is one of four basic proteins of the secretory granules of eosinophils. It has a variety of functions associated with inflammatory responses. Little is known about the causes for variation in serum ECP levels. Aim: To identify factors associated with variation in serum ECP and to determine the relative proportion of the variation in ECP due to genetic and non-genetic factors, in an adult twin sample. Methods: A sample of 575 twins, selected through a proband with self-reported asthma, had serum ECP, lung function, airway responsiveness to methacholine, exhaled nitric oxide, and skin test reactivity, measured. Linear regression analysis and variance component models were used to study factors associated with variation in ECP and the relative genetic influence on ECP levels. Results: Sex (regression coefficient = -0.107, P < 0.001), body mass index (BMI) (0.007, P = 0.028), and airway responsiveness to methacholine (0.074, P = 0.001) were significantly associated with ECP. Adjusted for these factors, ECP correlated 0.53 (P < 0.001) and 0.27 (P = 0.001) in monozygotic and dizygotic twins, respectively (P-value for difference = 0.05). According to the most parsimonious variance component model, genetic factors accounted for 57% (CI: 42-72%, P < 0.001) of the variance in ECP levels, whereas the remainder (43%) was ascribable to non-shared environmental factors. The genetic correlation between ECP and airway responsiveness to methacholine was statistically non-significant (r = -0.11, P = 0.50). Conclusion: Around half of all variance in serum ECP is explained by genetic factors. Serum ECP is influenced by sex, BMI, and airway responsiveness. Serum ECP and airway responsiveness seem not to share genetic variance

Cultured Mast Cells from Patients with Asthma and Controls Respond with Similar Sensitivity to Recombinant Der P2-Induced, IgE-Mediated Activation

The function of cultured mast cells may depend on genetic or environmental influence on the stem cell donor. This study investigates whether asthma or atopy in the donor influenced the growth and sensitivity of mast cells cultured from patients with asthma and healthy controls under identical conditions. Mast cells were cultured from peripheral blood from twelve patients with an objectively confirmed asthma diagnosis and eight healthy subjects. During the last 2weeks of culture, mast cells were incubated with IL-4 and 80kU/l recombinant human IgE containing two clones (7%+7%) specific for mite allergen Der p2. The sensitivity of IgE-mediated activation of mast cells was investigated as Fc epsilon RI-mediated upregulation of CD63. Ten subjects were atopic, defined as a positive skin prick test (>3mm) to at least one of ten common allergens. After activation with recombinant Der p2, the maximum CD63 median fluorescence intensity was 20 456 +/- 1640 (SE) for patients with asthma and 22 275 +/- 1971 (SE) for controls (ns). The fraction of CD63 positive cells was 54.4% in patients with asthma and 48.4% in controls (ns). The allergen concentration inducing 50% of the maximal CD63 response was similar in patients with asthma [-0.4795 log ng/ml +/- 0.092 (SE)] and controls (-0.6351 log ng/ml +/- 0.083, ns) and in atopic and non-atopic subjects. When cultured, sensitized and activated under identical conditions, mast cells from allergic asthmatics and healthy controls respond similar. Activation of cultured mast cells appears to depend on culture conditions (IL-4, IgE) rather than on donor status as atopy and asthma