CT Analysis of the Anterior Mediastinum in Idiopathic Pulmonary Fibrosis and Nonspecific Interstitial Pneumonia

OBJECTIVE: We wanted to determine whether the amount and shape of the anterior mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was different from those of the normal control group. MATERIALS AND METHODS: We selected patients who suffered with UIP (n = 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six controls were selected from individuals with normal CT findings and normal pulmonary function tests. All three groups (n = 78) were individually matched for age and gender. The amounts of anterior mediastinal fat, and the retrosternal anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat were compared by one-way analysis of variance and Bonferroni's test. The shapes of the anterior mediastinum were compared using the Chi-square test. Exact logistic regression analysis and polychotomous logistic regression analysis were employed to assess whether the patients with NSIP or UIP had a tendency to show a convex shape of their anterior mediastinal fat. RESULTS: The amount of anterior mediastinal fat was not different among the three groups (p = 0.175). For the UIP patients, the retrosternal AP dimension of the anterior mediastinal fat was shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat was longer (p = 0.001) than those of the normal control group. For the NSIP patients, only the transverse dimension was significantly longer than those of the normal control group (p < 0.001). The convex shape of the anterior mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-infinity, p < 0.001) and UIP (OR = 24.42, CI 4.06-infinity, p < 0.001). CONCLUSION: For UIP patients, the retrosternal AP and transverse dimensions are different from those of normal individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and NSIP patients have a tendency to have a convex shape of their anterior mediastinal fat.This study is supported by KISTEP, the Ministry of Science and Technology, Korea

Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD)

Alpha-1-antitrypsin (AAT) plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD). In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val), PiM2 (Arg101His), PiM3 (Glu376Asp), PiS (Glu264Val) and PiZ (Glu342Lys) SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3) and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms

Control of Allergic Rhinitis and Asthma Test (CARAT) can be used to assess individual patients over time

BACKGROUND: The Control of Allergic Rhinitis and Asthma Test (CARAT10) has been proposed as the first tool to implement the Allergic Rhinitis and its Impact on Asthma initiative guidelines in clinical practice. To serve this purpose, it must have adequate properties to assess the control of an individual over time. This study aimed to prospectively assess the test-retest reliability, responsiveness and longitudinal validity of CARAT10. METHODS: Adults with asthma and allergic rhinitis were enrolled at 4 outpatient clinics of Portuguese central hospitals. At each of the two visits, 4 to 6 weeks apart, patients filled out CARAT10 and additional questionnaires, followed by a medical evaluation blinded to the questionnaires' answers. RESULTS: From the 62 patients included, 51 patients completely filled out CARAT10 at both visits. The test-retest reliability, computed as an intra-class correlation coefficient, was 0.82. Regarding responsiveness, a significant change (p = 0.002) of CARAT10 score in clinically unstable patients was observed (95%CI -5.08; -1.31) and the Guyatt's responsiveness index was 1.54. As for the longitudinal validity assessment, the correlation coefficients of the changes of CARAT10 scores with those of ACQ5 and symptoms VAS ranged from 0.49 to 0.65, while with the physician assessment of control they ranged from 0.31 to 0.41. CONCLUSION: CARAT10 has good test-retest reliability, responsiveness and longitudinal validity. It can be used to assess control of allergic rhinitis and asthma, both to compare groups in clinical studies and to evaluate individual patients in clinical practice

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

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

Beyond a consensus classification for idiopathic interstitial pneumonias: progress and controversies

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74699/1/j.1365-2559.2008.03173.x.pd

Rapid effects of extrafine beclomethasone dipropionate/formoterol fixed combination inhaler on airway inflammation and bronchoconstriction in asthma: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The dose-dependent anti-inflammatory effects of a recent fixed combination of extrafine beclomethasone dipropionate/formoterol (BDP/F) were investigated using non-invasive markers of inflammation, exhaled nitric oxide (NO) and adenosine monophosphate (AMP) provocative challenge. The aim was to assess the onset of the anti-inflammatory action of low and high doses and evaluate the suitability of non-invasive assessments to demonstrate dose response.</p> <p>Methods</p> <p>Steroid naïve adult out-patients with mild asthma, sensitive to AMP with baseline exhaled NO > 25 parts per billion entered a double-blind, placebo-controlled, 3-way, cross-over study. Patients were randomised to low dose (1 actuation) or high dose (4 actuations) extrafine BDP/F 100/6 μg, or placebo administered twice daily on Days 1 and 2 and once in the morning on Day 3 of each period. Exhaled NO was measured pre-dose on Day 1, then 2 and 4 hours post-administration on Day 3. The AMP challenge was performed 4 hours post-administration on Day 3 and forced expiratory volume in 1 second (FEV₁, L) was measured from 0 to 4 hours post-dose on Day 1. Endpoints were NO at 2 and 4 hours, AMP challenge at 4 hours after the fifth dose on Day 3 and FEV₁area under the curve from 0 to 4 h post-dose on Day 1. Analysis of covariance was performed for NO and FEV₁and analysis of variance for AMP challenge.</p> <p>Results</p> <p>Eighteen patients were randomised and completed the study. Exhaled NO was significantly lower for both doses of extrafine BDP/F versus placebo at 2 and 4 hours (high dose LS mean difference: -22.5 ppb, p < 0.0001 and -20.5 ppb, p < 0.0001; low dose: -14.1 ppb, p = 0.0006 and -12.1 ppb, p = 0.0043) with a significant dose response (p = 0.0342 and p = 0.0423). Likewise, AMP challenge revealed statistically significant differences between both doses of extrafine BDP/F and placebo (high dose LS mean difference: 4.8 mg/mL, p < 0.0001; low dose: 3.7 mg/mL, p < 0.0001), and a significant dose response (p = 0.0185). FEV₁was significantly improved versus placebo for both doses (high dose LS mean difference: 0.2 L, p = 0.0001; low dose: 0.2 L p = 0.0001), but without a significant dose response.</p> <p>Conclusions</p> <p>The fixed combination inhaler of extrafine BDP/F has early dose-dependent anti-inflammatory effects with a rapid onset of bronchodilatation in mild asthmatic patients.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01343745">NCT01343745</a></p

IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study

Idiopathic pulmonary fibrosis (IPF) is a rare and devastating lung disease of unknown aetiology. Genetic variations in the IL1RN gene, encoding the interleukin-1 receptor antagonist (IL-1Ra), have been associated with IPF susceptibility. Several studies investigated the variable number tandem repeat (VNTR) or single nucleotide polymorphisms rs408392, rs419598 and rs2637988, with variable results. The aim of this study was to elucidate the influence of polymorphisms in IL1RN on IPF susceptibility and mRNA expression. We performed a meta-analysis of the five case–control studies that investigated an IL1RN polymorphism in IPF in a Caucasian population. In addition, we investigated whether IL1RN mRNA expression was influenced by IL1RN polymorphisms. The VNTR, rs408392 and rs419598 were in tight linkage disequilibrium, with D′ > 0.99. Furthermore, rs2637988 was in linkage disequilibrium with the VNTR (D′ = 0.90). A haploblock of VNTR*2 and the minor alleles of rs408392and rs419598 was constructed. Meta-analysis revealed that this VNTR*2 haploblock is associated with IPF susceptibility both with an allelic model (odds ratio = 1.42, p = 0.002) and a carriership model (odds ratio = 1.60, p = 0.002). IL1RN mRNA expression was significantly influenced by rs2637988, with lower levels found in carriers of the (minor) GG genotype (p < 0.001). From this meta-analysis, we conclude that the VNTR*2 haploblock is associated with susceptibility to IPF. In addition, polymorphisms in IL1RN influence IL-1Ra mRNA expression, suggesting that lower levels of IL-1Ra predispose to developing IPF. Together these findings demonstrate that the cytokine IL-1Ra plays a role in IPF pathogenesis

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