Reproducibility of exhaled nitric oxide in smokers and non-smokers: relevance for longitudinal studies

<p>Abstract</p> <p>Background</p> <p>Currently, there is much interest in measuring fractional exhaled nitric oxide (<b>FE_NO</b>) in populations. We evaluated the reproducibility of <b>FE_NO</b>in healthy subjects and determined the number of subjects necessary to carry out a longitudinal survey of <b>FE_NO</b>in a population containing smokers and non-smokers, based on the assessed reproducibility.</p> <p>Methods</p> <p>The reproducibility of <b>FE_NO</b>was examined in 18 healthy smokers and 21 non-smokers. <b>FE_NO</b>was assessed once at 9 AM on five consecutive days; in the last day this measurement was repeated at 2 PM. Respiratory symptoms and medical history were assessed by questionnaire. The within- and between-session repeatability of <b>FE_NO</b>and log-transformed <b>FE_NO</b>was described. The power of a longitudinal study based on a relative increase in <b>FE_NO</b>was estimated using a bilateral t-test of the log-transformed <b>FE_NO</b>using the between-session variance of the assay.</p> <p>Results</p> <p><b>FE_NO</b>measurements were highly reproducible throughout the study. <b>FE_NO</b>was significantly higher in males than females regardless of smoking status. <b>FE_NO</b>was positively associated with height (p < 0.001), gender (p < 0.034), smoking (p < 0.0001) and percent FEV₁/FVC (p < 0.001) but not with age (p = 0.987). The between-session standard deviation was roughly constant on the log scale. Assuming the between-session standard deviation is equal to its longitudinal equivalent, either 111 or 29 subjects would be necessary to achieve an 80% power in detecting a 3% or a 10% increase in <b>FE_NO</b>respectively.</p> <p>Conclusion</p> <p>The good reproducibility of <b>FE_NO</b>is not influenced by gender or smoking habits. In a well controlled, longitudinal study it should allow detecting even small increases in <b>FE_NO</b>with a reasonable population size.</p

Exhaled nitric oxide and urinary EPX levels in infants: a pilot study

<p>Abstract</p> <p>Background</p> <p>Objective markers of early airway inflammation in infants are not established but are of great interest in a scientific setting. Exhaled nitric oxide (FeNO) and urinary eosinophilic protein X (uEPX) are a two such interesting markers.</p> <p>Objective</p> <p>To investigate the feasibility of measuring FeNO and uEPX in infants and their mothers and to determine if any relations between these two variables and environmental factors can be seen in a small sample size. This was conducted as a pilot study for the ongoing Swedish Environmental Longitudinal Mother and child Asthma and allergy study (SELMA).</p> <p>Methods</p> <p>Consecutive infants between two and six months old and their mothers at children's health care centres were invited, and 110 mother-infant pairs participated. FeNO and uEPX were analysed in both mothers and infants. FeNO was analyzed in the mothers online by the use of the handheld Niox Mino device and in the infants offline from exhaled air sampled during tidal breathing. A 33-question multiple-choice questionnaire that dealt with symptoms of allergic disease, heredity, and housing characteristics was used.</p> <p>Results</p> <p>FeNO levels were reduced in infants with a history of upper respiratory symptoms during the previous two weeks (p < 0.002). There was a trend towards higher FeNO levels in infants with windowpane condensation in the home (p < 0.05). There was no association between uEPX in the infants and the other studied variables.</p> <p>Conclusion</p> <p>The use of uEPX as a marker of early inflammation was not supported. FeNO levels in infants were associated to windowpane condensation. Measuring FeNO by the present method may be an interesting way of evaluating early airway inflammation. In a major population study, however, the method is difficult to use, for practical reasons.</p

Prevalence of asthma symptoms based on the European Community Respiratory Health Survey questionnaire and FENO in university students: gender differences in symptoms and FENO

<p>Abstract</p> <p>Background</p> <p>The fractional concentration of nitric oxide in exhaled air (F<smcaps>E</smcaps>NO) is used as a biomarker of eosinophilic airway inflammation. F<smcaps>E</smcaps>NO is increased in patients with asthma. The relationship between subjective asthma symptoms and airway inflammation is an important issue. We expected that the subjective asthma symptoms in women might be different from those in men. Therefore, we investigated the gender differences of asthma symptoms and F<smcaps>E</smcaps>NO in a survey of asthma prevalence in university students.</p> <p>Methods</p> <p>The information about asthma symptoms was obtained from answers to the European Community Respiratory Health Survey (ECRHS) questionnaire, and F<smcaps>E</smcaps>NO was measured by an offline method in 640 students who were informed of this study and consented to participate.</p> <p>Results</p> <p>The prevalence of asthma symptoms on the basis of data obtained from 584 students (266 men and 318 women), ranging in age from 18 to 24 years, was analyzed. Wheeze, chest tightness, an attack of shortness of breath, or an attack of cough within the last year was observed in 13.2% of 584 students. When 38.0 ppb was used as the cut-off value of F<smcaps>E</smcaps>NO to make the diagnosis of asthma, the sensitivity was 86.8% and the specificity was 74.0%. F<smcaps>E</smcaps>NO was ≥ 38.0 ppb in 32.7% of students. F<smcaps>E</smcaps>NO was higher in men than in women. The prevalence of asthma symptoms estimated by considering F<smcaps>E</smcaps>NO was 7.2%; the prevalence was greater in men (9.4%) than women (5.3%). A F<smcaps>E</smcaps>NO ≥ 38.0 ppb was common in students who reported wheeze, but not in students, especially women, who reported cough attacks.</p> <p>Conclusions</p> <p>The prevalence of asthma symptoms in university students age 18 to 24 years in Japan was estimated to be 7.2% on the basis of F<smcaps>E</smcaps>NO levels as well as subjective symptoms. Gender differences were observed in both F<smcaps>E</smcaps>NO levels and asthma symptoms reflecting the presence of eosinophilic airway inflammation.</p> <p>Trial registration number</p> <p>UMIN000003244</p

Associations of airway inflammation and responsiveness markers in non asthmatic subjects at start of apprenticeship

<p>Abstract</p> <p>Background</p> <p>Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma?</p> <p>Methods</p> <p>Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed.</p> <p>Results</p> <p>Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy.</p> <p>Conclusions</p> <p>Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question.</p

Computer-assisted detection of pulmonary embolism: evaluation of pulmonary CT angiograms performed in an on-call setting

Item does not contain fulltextPURPOSE: The purpose of the study was to assess the stand-alone performance of computer-assisted detection (CAD) for evaluation of pulmonary CT angiograms (CTPA) performed in an on-call setting. METHODS: In this institutional review board-approved study, we retrospectively included 292 consecutive CTPA performed during night shifts and weekends over a period of 16 months. Original reports were compared with a dedicated CAD system for pulmonary emboli (PE). A reference standard for the presence of PE was established using independent evaluation by two readers and consultation of a third experienced radiologist in discordant cases. RESULTS: Original reports had described 225 negative studies and 67 positive studies for PE. CAD found PE in seven patients originally reported as negative but identified by independent evaluation: emboli were located in segmental (n = 2) and subsegmental arteries (n = 5). The negative predictive value (NPV) of the CAD algorithm was 92% (44/48). On average there were 4.7 false positives (FP) per examination (median 2, range 0-42). In 72% of studies or=10 FP. CONCLUSION: CAD identified small emboli originally missed under clinical conditions and found 93% of the isolated subsegmental emboli. On average there were 4.7 FP per examination.1 april 201

Study circles improve the precision in nutritional care in special accommodations

Background: Disease-related malnutrition is a major health problem in the elderly population, but it has until recently received very little attention, especially are management issues under-explored. By identifying residents at the risk of undernutrition, appropriate nutritional care can be provided. Objectives: Do study circles and policy documents improve the precision in nutritional care and decrease the prevalence of low or high BMI? Design: Pre and post intervention study. Setting: Special accommodations (nursing homes) within six municipalities were involved. Participants: In 2005, 1726 (90.4%) out of 1910 residents agreed to participate and in 2007, 1526 (81.8%) out of 1866 residents participated. Intervention: Study circles in one municipality, having a policy document in one municipality and no intervention in four municipalities. Measurements: Risk of undernutrition was defined as involving any of: involuntary weight loss, low BMI, and/or eating difficulties. Overweight was defined as high BMI. Results: In 2005 and 2007, 64% of 1726 and 66% of 1526 residents respectively were at the risk of undernutrition. In 2007 significantly more patients in the study circle municipality were accurately provided protein and energy enriched food compared to in the no intervention municipalities. There was a decrease in the prevalence of low BMI in the study circle municipality and the prevalence of overweight increased in the policy document municipality between 2005 and 2007

Exhaled nitric oxide in a population-based study of Southern California Schoolchildren

<p>Abstract</p> <p>Background</p> <p>Determinants of exhaled nitric oxide (FeNO) need to be understood better to maximize the value of FeNO measurement in clinical practice and research. Our aim was to identify significant predictors of FeNO in an initial cross-sectional survey of southern California schoolchildren, part of a larger longitudinal study of asthma incidence.</p> <p>Methods</p> <p>During one school year, we measured FeNO at 100 ml/sec flow, using a validated offline technique, in 2568 children of age 7–10 yr. We estimated online (50 ml/sec flow) FeNO using a prediction equation from a separate smaller study with adjustment for offline measurement artifacts, and analyzed its relationship to clinical and demographic characteristics.</p> <p>Results</p> <p>FeNO was lognormally distributed with geometric means ranging from 11 ppb in children without atopy or asthma to 16 ppb in children with allergic asthma. Although effects of atopy and asthma were highly significant, ranges of FeNO for children with and without those conditions overlapped substantially. FeNO was significantly higher in subjects aged > 9, compared to younger subjects. Asian-American boys showed significantly higher FeNO than children of all other sex/ethnic groups; Hispanics and African-Americans of both sexes averaged slightly higher than non-Hispanic whites. Increasing height-for-age had no significant effect, but increasing weight-for-height was associated with decreasing FeNO.</p> <p>Conclusion</p> <p>FeNO measured offline is a useful biomarker for airway inflammation in large population-based studies. Further investigation of age, ethnicity, body-size, and genetic influences is needed, since they may contribute to substantial variation in FeNO.</p

Factors affecting exhaled nitric oxide measurements: the effect of sex

<p>Abstract</p> <p>Background</p> <p>Exhaled nitric oxide (F_ENO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F_ENO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F_ENO in a well characterised adult population.</p> <p>Methods</p> <p>Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F_ENO were explored by unadjusted and adjusted linear regression analyses.</p> <p>Results</p> <p>The effect of sex on F_ENO was both statistically and clinically significant, with F_ENO levels approximately 25% less in females. Overall, current smoking reduced F_ENO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F_ENO measurement. Atopy increased F_ENO by 60%. The sex-related differences in F_ENO remained significant (p < 0.001) after controlling for all other significant factors affecting F_ENO.</p> <p>Conclusion</p> <p>Even after adjustment, F_ENO values are significantly different in males and females. The derivation of reference values and the interpretation of F_ENO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.</p

Bronchial Responsiveness Is Related to Increased Exhaled NO (FENO) in Non-Smokers and Decreased FENO in Smokers

Rationale Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FENO), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role. Objectives To investigate how the relation between FENO and bronchial responsiveness is modulated by atopy and smoking habits. Methods Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed. Main Results Increased bronchial responsiveness was associated with increased FENO levels in non-smokers (p = 0.02) and decreased FENO levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FENO was seen only in the group smoking less &lt;10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FENO in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FENO and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values&lt;0.05). Conclusions The present study highlights the interactions of the relationship between FENO and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness

Genetic Variants in FBN-1 and Risk for Thoracic Aortic Aneurysm and Dissection.

OBJECTIVES: A recent genome wide association study (GWAS) by LeMaire et al. found that two single nucleotide polymorphisms (SNPs), rs2118181 and rs10519177 in the FBN-1 gene (encoding Fibrillin-1), were associated with thoracic aortic dissection (TAD), non-dissecting thoracic aortic aneurysm (TAA), and thoracic aortic aneurysm or dissection (TAAD); the largest effect was observed for the association of rs2118181 with TAD. We investigated whether rs2118181 and rs10519177 were associated with TAD, TAA, and TAAD in the Yale study. METHODS: The genotypes of rs2118181 and rs10519177 were determined for participants in the Yale study: 637 TAAD cases (140 TAD, 497 TAA) and 275 controls from the United States, Hungary, and Greece. The association of the genotypes with TAD, TAA and TAAD were assessed using logistic regression models adjusted for sex, age, study center and hypertension. RESULTS AND CONCLUSIONS: In the Yale study, rs2118181 was associated with TAD: compared with non-carriers, carriers of the risk allele had an unadjusted odds ratio for TAD of 1.80 (95% CI 1.15-2.80) and they had odds ratio for TAD of 1.87 (95% CI 1.09-3.20) after adjusting for sex, age, study center and hypertension. We did not find significant differences in aortic size, a potential confounder for TAD, between rs2118181 risk variant carriers and non-carriers: mean aortic size was 5.56 (95% CI: 5.37-5.73) for risk variant carriers (CC+CT) and was 5.48 (95% CI: 5.36-5.61) for noncarriers (TT) (p = 0.56). rs2118181 was not associated with TAA or TAAD. rs10519177 was not associated with TAD, TAA, or TAAD in the Yale study. Thus, the Yale study provided further support for the association of the FBN-1 rs2118181SNP with TAD