Susceptibility to chronic mucus hypersecretion, a genome wide association study

Background: Chronic mucus hypersecretion (CMH) is associated with an increased frequency of respiratory infections, excess lung function decline, and increased hospitalisation and mortality rates in the general population. It is associated with smoking, but it is unknown why only a minority of smokers develops CMH. A plausible explanation for this phenomenon is a predisposing genetic constitution. Therefore, we performed a genome wide association (GWA) study of CMH in Caucasian populations.Methods: GWA analysis was performed in the NELSON-study using the Illumina 610 array, followed by replication and metaanalysis in 11 additional cohorts. In total 2,704 subjects with, and 7,624 subjects without CMH were included, all current or former heavy smokers (&gt;= 20 pack-years). Additional studies were performed to test the functional relevance of the most significant single nucleotide polymorphism (SNP).Results: A strong association with CMH, consistent across all cohorts, was observed with rs6577641 (p = 4.25610(-6), OR = 1.17), located in intron 9 of the special AT-rich sequence-binding protein 1 locus (SATB1) on chromosome 3. The risk allele (G) was associated with higher mRNA expression of SATB1 (4.3610 29) in lung tissue. Presence of CMH was associated with increased SATB1 mRNA expression in bronchial biopsies from COPD patients. SATB1 expression was induced during differentiation of primary human bronchial epithelial cells in culture.Conclusions: Our findings, that SNP rs6577641 is associated with CMH in multiple cohorts and is a cis-eQTL for SATB1, together with our additional observation that SATB1 expression increases during epithelial differentiation provide suggestive evidence that SATB1 is a gene that affects CMH.</p

Quantitative Computed Tomography in COPD: Possibilities and Limitations

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment. Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions. This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD

Determination of regional lung air volume distribution at mid-tidal breathing from computed tomography: A retrospective study of normal variability and reproducibility

© 2014 Fleming et al.; licensee BioMed Central Ltd. Background: Determination of regional lung air volume has several clinical applications. This study investigates the use of mid-tidal breathing CT scans to provide regional lung volume data.Methods: Low resolution CT scans of the thorax were obtained during tidal breathing in 11 healthy control male subjects, each on two separate occasions. A 3D map of air volume was derived, and total lung volume calculated. The regional distribution of air volume from centre to periphery of the lung was analysed using a radial transform and also using one dimensional profiles in three orthogonal directions.Results: The total air volumes for the right and left lungs were 1035 +/- 280 ml and 864 +/- 315 ml, respectively (mean and SD). The corresponding fractional air volume concentrations (FAVC) were 0.680 +/- 0.044 and 0.658 +/- 0.062. All differences between the right and left lung were highly significant (p < 0.0001). The coefficients of variation of repeated measurement of right and left lung air volumes and FAVC were 6.5% and 6.9% and 2.5% and 3.6%, respectively. FAVC correlated significantly with lung space volume (r = 0.78) (p < 0.005). FAVC increased from the centre towards the periphery of the lung. Central to peripheral ratios were significantly higher for the right (0.100 +/- 0.007 SD) than the left (0.089 +/- 0.013 SD) (p < 0.0001).Conclusion: A technique for measuring the distribution of air volume in the lung at mid-tidal breathing is described. Mean values and reproducibility are described for healthy male control subjects. Fractional air volume concentration is shown to increase with lung size.Air Liquid

Change in pulmonary diffusion capacity in a general population sample over 9 years

Rationale: Data on the change in diffusion capacity of the lung for carbon monoxide (DL_CO) over time are limited. We aimed to examine change in DL_CO (ΔDL_CO) over a 9-year period and its predictors. Methods: A Norwegian community sample comprising 1,152 subjects aged 18–73 years was examined in 1987 and 1988. Of the 1,109 subjects still alive, 830 (75%) were re-examined in 1996/97. DL_CO was measured with the single breath-holding technique. Covariables recorded at baseline included sex, age, height, weight, smoking status, pack years, occupational exposure, educational level, and spirometry. Generalized estimating equations analyses were performed to examine relations between ΔDL_CO and the covariables. Results: At baseline, mean [standard deviation (SD)] DL_CO was 10.8 (2.4) and 7.8 (1.6) mmol·min−1·kPa−1 in men and women, respectively. Mean (SD) ΔDLCO was −0.24 (1.31) mmol·min^−1·kPa^−1. ΔDL_CO was negatively related to baseline age, DL_CO, current smoking, and pack years, and positively related to forced expiratory volume in 1 second (FEV_1) and weight. Sex, occupational exposure, and educational level were not related to ΔDL_CO. Conclusions: In a community sample, more rapid decline in DL_CO during 9 years of observation time was related to higher age, baseline current smoking, more pack years, larger weight, and lower FEV_1