CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India

CONTEXT:

CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes.

AIMS:

The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India.

SETTINGS AND DESIGN:

Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined.

MATERIALS AND METHODS:

Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the polymorphism of C-159T.

RESULTS:

The genotype and allelic frequencies were in Hardy-Weinberg’s equilibrium. Prevalence of CC, CT, and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and 5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and 5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD) patients; whereas the control cohort with no methyl isocyanate exposure displayed (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR] =2.61 and 2.02 respectively).

CONCLUSION:

COPD risk significantly found among those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40 respectively). Therefore, single nucleotide polymorphism (SNP) C-159T polymorphism in CD14 gene might be a risk factor for development of CLD in this population.     

Inbreeding as a cause for deafness: Dadhkai study

BACKGROUND:

We report on the higher prevalence of deaf-mutes from a village in Jammu and Kashmir State of India.

MATERIALS AND METHODS:

A cross-sectional study among 79 deaf mutes using pedigree analysis, audiometry, imaging and molecular analysis.

RESULTS:

A high rate of hereditary deafness with 79 individuals diagnosed to be suffering from non-syndrome deafness in a total population of 2452 individuals residing in the village.

INTERPRETATION:

Flourishing of intermarriages led to a population with high prevalence of deafness     

Cluster Analysis in Patients with GOLD 1 Chronic Obstructive Pulmonary Disease

Background

We hypothesized that heterogeneity exists within the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 spirometric category and that different subgroups could be identified within this GOLD category.

Methods

Pre-randomization study participants from two clinical trials were symptomatic/asymptomatic GOLD 1 chronic obstructive pulmonary disease (COPD) patients and healthy controls. A hierarchical cluster analysis used pre-randomization demographics, symptom scores, lung function, peak exercise response and daily physical activity levels to derive population subgroups.

Results

Considerable heterogeneity existed for clinical variables among patients with GOLD 1 COPD. All parameters, except forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC), had considerable overlap between GOLD 1 COPD and controls. Three-clusters were identified: cluster I (18 [15%] COPD patients; 105 [85%] controls); cluster II (45 [80%] COPD patients; 11 [20%] controls); and cluster III (22 [92%] COPD patients; 2 [8%] controls). Apart from reduced diffusion capacity and lower baseline dyspnea index versus controls, cluster I COPD patients had otherwise preserved lung volumes, exercise capacity and physical activity levels. Cluster II COPD patients had a higher smoking history and greater hyperinflation versus cluster I COPD patients. Cluster III COPD patients had reduced physical activity versus controls and clusters I and II COPD patients, and lower FEV₁/FVC versus clusters I and II COPD patients.

Conclusions

The results emphasize heterogeneity within GOLD 1 COPD, supporting an individualized therapeutic approach to patients.

Trial registration

www.clinicaltrials.gov. NCT01360788 and NCT01072396.     

The effect of aging on micronuclei frequency and proliferation in human peripheral blood lymphocytes

INTRODUCTION:

Increase in the instability of cellular genome with an increasing age is the result of an accumulation of cellular damage and mutations. This instability which might be observed as chromosome damage or chromosome losses can be measured by the micronucleus technique.

AIM:

The aim of this study was to investigate the effect of aging and oxidative stress induced by non-toxic levels of H₂O₂ on micronuclei induction and their relationship to cell proliferation in human peripheral blood lymphocytes.

MATERIALS AND METHODS:

Healthy volunteers with different ages were choosen. Spontaneous and H₂O₂ induced micronuclei frequencies were measured in peripheral blood lymphocytes of 30 volunteers by the micronucleus method.

RESULTS:

Spontaneous micronuclei frequencies increased first then started to decrease after 50 years of age. This biphasic response was significantly higher than micronucleus (MN) frequencies induced by H₂O₂ (P < 0.05), which followed the similar shape of response to increasing ages with lower frequencies. Proliferative capacity of cells either treated with H₂O₂ or not did not differ with an increasing age giving similar responses.

CONCLUSION:

These results indicate biphasic character of chromosome damage; first increase and decrease after 50 years with an increasing age. But this change pattern was not correlated with the steady state of proliferation capacity of cells through an increasing age. Decreases in H₂O₂-induced MN frequencies compared to spontaneous MN frequencies may be inducing an apoptosis by H₂O₂ treatment leading to underscoring damaged cells.     

Linkage analysis of three families with arrythmogenic right ventricular cardiomyopathy in India

BACKGROUND:

Arrythmogenic Right Ventricular Cardiomyopathy (ARVC) is a primary myocardial disorder morphologically characterized by subtle to severe replacement of the right ventricular myocardium by fatty and fibrous tissue. ARVC is known to be highly prevalent in European population with recent reports implicating it to be a major cause of sudden death in young individuals even from American and Asian population.

AIM:

To implicate or exclude TMEM43 (ARVC-5), DSP(ARVC-8) genes and the yet to be identified gene at ARVC-6 locus in the pathogenesis in three families affected with ARVC from India.

MATERIALS AND METHODS:

Three families comprising of 42 affected/unaffected members were included in the study. Three microsatellite markers, D3S3613 (ARVC5) D10S1664 (ARVC6), D6S309 (ARVC8) were genotyped by PCR-based native PAGE. Two-point Linkage analysis was performed using LINKAGE program version 5.2

RESULTS AND DISCUSSION:

LOD scores from linkage analysis for the microsatellite marker D10S1664 (ARVC-6) in families KS and REV have shown positive value hinting the involvement of this locus in the etiology of ARVC, while linkage analysis in the SB family ruled out involvement of DSP, TMEM43 and ARVC-6, as negative LOD scores were obtained with all three loci. Therefore, linkage analysis carried out in the present study indicates that ARVC-6 (cumulative LOD score is equal to plus 1.203376 at θ is equal to 0.05) could be the locus harboring the mutated gene in two out of three families.     

Angiotensin II type 1 receptor A1166C gene polymorphism and essential hypertension in Calabar and Uyo cities,Nigeria

OBJECTIVES:

The angiotensin II protein is a vasoconstrictor that exerts most of its influence through the angiotensin II type 1 receptor (AT₁R). Inconsistent association between the A1166C polymorphism of the AT₁R gene and hypertension has been reported among various populations but not among the peoples of Calabar and Uyo. This study was designed to determine the frequency of the A1166C polymorphism of the AT₁R gene and its association with hypertension in a sample population of Calabar and Uyo.

MATERIALS AND METHODS:

A population-based case control design consisting of total of 1224 participants, 612 each of patients and controls were randomly recruited from hypertension clinics and the general population. Genotyping of the A1166C allele of the AT₁R gene to identify variants was performed using polymerase chain reaction and restriction enzyme digestion. Multiple regressions were applied to test whether the A1166 genotypes were predictors of hypertension.

RESULTS:

99% of the study population had the wild type AA genotype, and 1% was AC heterozygous carriers of the A1166C polymorphism.

CONCLUSION:

The A1166C polymorphism was not a predictor of hypertension in the sample population of Calabar and Uyo.     

Fast and cost-effective mining of microsatellite markers using NGS technology: an example of a Korean water deer Hydropotes inermis argyropus

Background

Microsatellites, a special class of repetitive DNA sequence, have become one of the most popular genetic markers for population/conservation genetic studies. However, its application to endangered species has been impeded by high development costs, a lack of available sequences, and technical difficulties. The water deer Hydropotes inermis is the sole existing endangered species of the subfamily Capreolinae. Although population genetics studies are urgently required for conservation management, no species-specific microsatellite marker has been reported.

Methods

We adopted next-generation sequencing (NGS) to elucidate the microsatellite markers of Korean water deer and overcome these impediments on marker developments. We performed genotyping to determine the efficiency of this method as applied to population genetics.

Results

We obtained 98 Mbp of nucleotide information from 260,467 sequence reads. A total of 20,101 di-/tri-nucleotide repeat motifs were identified; di-repeats were 5.9-fold more common than tri-repeats. [CA]_n and [AAC]_n/[AAT]_n repeats were the most frequent di- and tri-repeats, respectively. Of the 17,206 di-repeats, 12,471 microsatellite primer pairs were derived. PCR amplification of 400 primer pairs yielded 106 amplicons and 79 polymorphic markers from 20 individual Korean water deer. Polymorphic rates of the 79 new microsatellites varied from 2 to 11 alleles per locus (H_e: 0.050–0.880; H_o: 0.000–1.000), while those of known microsatellite markers transferred from cattle to Chinese water deer ranged from 4 to 6 alleles per locus (H_e: 0.279–0.714; H_o: 0.300–0.400).

Conclusions

Polymorphic microsatellite markers from Korean water deer were successfully identified using NGS without any prior sequence information and deposited into the public database. Thus, the methods described herein represent a rapid and low-cost way to investigate the population genetics of endangered/non-model species.     

Airway inflammation and mannitol challenge test in COPD

Background

Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled mannitol captures eosinophilia in induced sputum in COPD.

Methods

Twenty-eight patients (age 58 ± 7.8 yr, packyears 40 ± 15.5, post-bronchodilator FEV₁ 77 ± 14.0%predicted, no inhaled steroids ≥4 wks) with mild-moderate COPD (GOLD I-II) completed two randomized visits with hypertonic saline-induced sputum and mannitol challenge (including sputum collection). AHR to mannitol was expressed as response-dose-ratio (RDR) and related to cell counts, ECP, MPO and IL-8 levels in sputum.

Results

There was a positive correlation between RDR to mannitol and eosinophil numbers (r = 0.47, p = 0.03) and level of IL-8 (r = 0.46, p = 0.04) in hypertonic saline-induced sputum. Furthermore, significant correlations were found between RDR and eosinophil numbers (r = 0.71, p = 0.001), level of ECP (r = 0.72, p = 0.001), IL-8 (r = 0.57, p = 0.015) and MPO (r = 0.64, p = 0.007) in sputum collected after mannitol challenge. ROC-curves showed 60% sensitivity and 100% specificity of RDR for >2.5% eosinophils in mannitol-induced sputum.

Conclusions

In mild-moderate COPD mannitol hyperresponsiveness is associated with biomarkers of airway inflammation. The high specificity of mannitol challenge suggests that the test is particularly suitable to exclude eosinophilic airways inflammation, which may facilitate individualized treatment in COPD.

Trial registration

Netherlands Trial Register (NTR): NTR1283     

The clinical features of the overlap between COPD and asthma

Background

The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.

Methods

We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.

Results

119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.

Conclusion

Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00608764","term_id":"NCT00608764"}}NCT00608764     

Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

Background

The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Methods

In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843) and II (n = 804), patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV₁)/forced vital capacity ratio of ≤70% and FEV₁ <80% of the predicted value. The primary endpoint was trough FEV₁ at 12 and 28 weeks. Secondary endpoints were health status measured by St George''s Respiratory Questionnaire (SGRQ) and time to first moderate or severe COPD exacerbation.

Results

At 12 and 28 weeks, aclidinium improved trough FEV₁ versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p < 0.001) and ACCLAIM/COPD II (by 63 and 59 mL; both p < 0.001). More patients had a SGRQ improvement ≥4 units at 52 weeks with aclidinium versus placebo in ACCLAIM/COPD I (48.1% versus 39.5%; p = 0.025) and ACCLAIM/COPD II (39.0% versus 32.8%; p = 0.074). The time to first exacerbation was significantly delayed by aclidinium in ACCLAIM/COPD II (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.55 to 0.92; p = 0.01), but not ACCLAIM/COPD I (HR 1.0; 95% CI 0.72 to 1.33; p = 0.9). Adverse events were minor in both studies.

Conclusion

Aclidinium is effective and well tolerated in patients with moderate to severe COPD.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00363896","term_id":"NCT00363896"}}NCT00363896 (ACCLAIM/COPD I) and {"type":"clinical-trial","attrs":{"text":"NCT00358436","term_id":"NCT00358436"}}NCT00358436 (ACCLAIM/COPD II).     

Prevalence of methylenetetrahydrofolate reductase C677T polymorphism in eastern Uttar Pradesh

AIM:

This study was aimed to evaluate the 5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation in eastern Uttar Pradesh population.

MATERIALS AND METHODS:

Polymerase chain reaction (PCR) using specific primers followed by amplicon digestion by Hinf I restriction enzyme was used for MTHFR C677T polymorphism analysis. Total 250 subjects were analyzed.

RESULTS:

The CC genotype was found in 192 subjects, followed by CT in 56 subjects and TT in 2 subject. Genotype frequencies of CC, CT and TT were 0.768, 0.224 and 0.008, respectively. The frequency of C allele was found to be 0.88 and that of T allele was 0.12.

CONCLUSION:

It is evident from the results of the present study that the percentage of homozygous genotype (CC) is highest in the target population.     

Recombination in human leukocyte antigen region in two Asian Indian families

BACKGROUND:

Recombination (crossing over) may generate novel haplotypes that can be beneficial to a population against recently introduced pathogens. It may lead to the generation of new alleles.

SETTINGS AND DESIGN:

A prospective study at a tertiary care centre.

AIM:

To report two rare cases of crossing over in HLA region.

MATERIALS AND METHODS:

Tissue-typing was done by sequence specific primers (SSP) for DR locus and by both SSP and serology for Class I which was reconfirmed on fresh samples.

RESULTS:

In one patient crossing over had taken place in the region of A locus resulting in inheritance of A*01 instead of expected A*11. In second family crossing over had taken place in region of DRB1 locus and the sibling inherited DRB1*08 instead of DRB1*10.

CONCLUSIONS:

Possibility of recombination must be considered when interpreting implausible tissue-typing results of families worked up for BMT.     

Imbalance of dendritic cell co-stimulation in COPD

Background

Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.

Methods

Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV₁: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.

Results

Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function. In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.

Conclusion

An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0174-x) contains supplementary material, which is available to authorized users.     

Childhood pneumonia increases risk for chronic obstructive pulmonary disease: the COPDGene study

Background

Development of adult respiratory disease is influenced by events in childhood. The impact of childhood pneumonia on chronic obstructive pulmonary disease (COPD) is not well defined. We hypothesize that childhood pneumonia is a risk factor for reduced lung function and COPD in adult smokers.

Methods

COPD cases and control smokers between 45–80 years old from the United States COPDGene Study were included. Childhood pneumonia was defined by self-report of pneumonia at <16 years. Subjects with lung disease other than COPD or asthma were excluded. Smokers with and without childhood pneumonia were compared on measures of respiratory disease, lung function, and quantitative analysis of chest CT scans.

Results

Of 10,192 adult smokers, 854 (8.4 %) reported pneumonia in childhood. Childhood pneumonia was associated with COPD (OR 1.40; 95 % CI 1.17-1.66), chronic bronchitis, increased COPD exacerbations, and lower lung function: post-bronchodilator FEV₁ (69.1 vs. 77.1 % predicted), FVC (82.7 vs. 87.4 % predicted), FEV₁/FVC ratio (0.63 vs. 0.67; p < 0.001 for all comparisons). Childhood pneumonia was associated with increased airway wall thickness on CT, without significant difference in emphysema. Having both pneumonia and asthma in childhood further increased the risk of developing COPD (OR 1.85; 95 % CI 1.10-3.18).

Conclusions

Children with pneumonia are at increased risk for future smoking-related lung disease including COPD and decreased lung function. This association is supported by airway changes on chest CT scans. Childhood pneumonia may be an important factor in the early origins of COPD, and the combination of pneumonia and asthma in childhood may pose the greatest risk.

Clinical trials registration

ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00608764","term_id":"NCT00608764"}}NCT00608764 (Active since January 28, 2008).

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0273-8) contains supplementary material, which is available to authorized users.     

Missense mutation G296S in GATA4 is not responsible for cardiac septal defects

BACKGROUND:

The most common type of congenital heart disease is the cardiac septal defects, which has reported to be caused by a missense mutation (G296S) in exon 3 of the GATA4 gene.

AIMS:

The present study was undertaken to find out whether GATA4 gene is the prime cause of the septal defects in Mysore population.

MATERIALS AND METHODS:

GATA4 gene analyses were undertaken on 21 confirmed CHD cases by PCR and DNA sequencing.

RESULTS AND CONCLUSION:

Analysis of this particular mutation in 21 septal defect patients revealed that none of the patients had the mutation, indicating that this mutation is population specific or septal defect in Mysore population is caused due to mutations in other regions of the GATA4 gene.     

Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study

Background

Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD).

Methods

We genotyped 9131 individuals from the adult Danish population for cystic fibrosis 5T, 7T, 9T, and F508del alleles, and examined associations between 11 different genotype combinations, and annual FEV₁ decline and risk of asthma or COPD.

Results

5T heterozygotes vs. 7T homozygous controls had no increase in annual FEV₁ decline, self-reported asthma, spirometry-defined COPD, or incidence of hospitalization from asthma or COPD. In 5T/7T heterozygotes vs. 7T homozygous controls we had 90% power to detect an increase in FEV₁ decline of 8 ml, an odds ratio for self-reported asthma and spirometry-defined COPD of 1.9 and 1.7, and a hazard ratio for asthma and COPD hospitalization of 1.8 and 1.6, respectively. Both 5T homozygotes identified in the study showed evidence of asthma, while none of four 5T/F508del compound heterozygotes had severe pulmonary disease. 7T/9T individuals had annual decline in FEV₁ of 19 ml compared with 21 ml in 7T homozygous controls (t-test:P = 0.03). 6.7% of 7T homozygotes without an F508del allele in the cystic fibrosis transmembrane conductance regulator gene reported asthma vs. 11% of 7T/9T individuals with an F508del allele (χ²:P = 0.01) and 40% of 7T homozygotes with an F508del allele (P = 0.04). 7T homozygotes with vs. without an F508del allele also had higher incidence of asthma hospitalization (log-rank:P = 0.003); unadjusted and adjusted equivalent hazard ratios for asthma hospitalization were 11 (95%CI:1.5–78) and 6.3 (0.84–47) in 7T homozygotes with vs. without an F508del allele.

Conclusion

Polythymidine 5T heterozygosity is not associated with pulmonary dysfunction or disease in the adult Caucasian population. Furthermore, our results support that F508del heterozygosity is associated with increased asthma risk independently of the 5T allele.     

Derivation of normative data for the COPD assessment test (CAT)

Background

The tradition classification of the severity of COPD, based on spirometry, fails to encompass the heterogeneity of the disease. The COPD assessment test (CAT), a multi-dimensional, patient-filled questionnaire, assesses the overall health status of patients, and is recommended as part of the assessment of individuals with COPD. However, information regarding the range of values for the test in a non-COPD population (normative values) is limited, and consequently, knowledge regarding the optimal cut-off, and the minimum clinically important difference (MCID) for the test remain largely empirical.

Methods

CanCOLD is a population-based multi-center cohort study conducted across Canada, the methodology of which is based on the international BOLD initiative. The study includes subjects with COPD, at-risk individuals who smoke, and healthy control subjects. CAT questionnaires were administered at baseline to all subjects. Among non-COPD subjects, normative values for the CAT questionnaire, and psychometric properties of the test were characterized. Predictors of high CAT scores were identified using multivariable logistic regression.

Results

Of the 525 non-COPD subjects enrolled, 500 were included in the analysis. Mean FEV₁/FVC ratio among the 500 included subjects was 0.77 (SD 0.49); the mean predicted FEV₁ was 99.38% (SD 16.88%). The overall mean CAT score was 6 (SD 5.09); scores were higher among females (6.43, SD 5.59), and subjects over 80 years of age (mean 7.58, SD 6.82). Cronbach alpha for the CAT was 0.79, suggesting a high internal consistency for the test. A score of 16 was the 95th percentile for the population, and 27 subjects (5.4%) were found to have a CAT score > =16. Current smoking (aOR 3.41, 95% CI 1.05, 11.02), subject-reported physician-diagnosed asthma (aOR 7.59, 95% CI 2.71, 21.25) and musculoskeletal disease (aOR 4.09, 95% CI 1.72, 9.71) were found to be significantly associated with a score ≥16.

Conclusions

The characterization of CAT scores in the general population will be useful for norm-based comparisons. Longitudinal follow-up of these subjects will help in the optimization of cut-offs for the test.     

Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers

Rationale

Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear.

Objectives

To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DL_CO) corrected for alveolar volume (K_CO).

Methods

Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD).

Measurements and Main Results

Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low K_CO had lower ASMMI values compared to those with normal K_CO. Moreover, female smokers with low K_CO, had lower BMD and shorter TL compared to those with normal K_CO.

Conclusions

Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a K_CO decrease. Decreased K_CO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.     

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

Methods

We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers with at least moderate airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV₁/FVC) <0.7 and FEV₁ < 80% predicted on post-bronchodilator spirometry. TLC was calculated by using volumetric computed tomography scans at full inspiration (TLC_CT). Genotyping in each cohort was completed, with statistical imputation of additional markers. To find genetic variants associated with TLC_CT, linear regression models were used, with adjustment for age, sex, pack-years of smoking, height, and principal components for genetic ancestry. Results were summarized using fixed-effect meta-analysis.

Results

Analysis of a total of 4,543 COPD subjects identified one genome-wide significant locus on chromosome 5p15.2 (rs114929486, β = 0.42L, P = 4.66 × 10⁻⁸).

Conclusions

In COPD, TLC_CT was associated with a SNP in dynein, axonemal, heavy chain 5 (DNAH5), a gene in which genetic variants can cause primary ciliary dyskinesia. DNAH5 could have an effect on hyperinflation in COPD.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0097-y) contains supplementary material, which is available to authorized users.     

The NQO1 allelic frequency in hindu population of central India varies from that of other Asian populations

CONTEXT:

The enzymes encoded by the polymorphic genes NAD (P) H: quinone oxidoreductase 1 (NQO1) play an important role in the activation and inactivation of xenobiotics. This enzyme has been associated with xenobiotic related diseases, such as cancer, therapeutic failure and abnormal effects of drugs.

AIM:

The aim of the present study was to determine the allelic and genotypic frequencies of NQO Hinf I polymorphisms in a Hindu population of Central India.

SETTINGS AND DESIGN:

Polymorphisms of NQO1 were determined in 311 unrelated Hindu individuals.

MATERIALS AND METHODS:

Polymerase chain reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) analysis in peripheral blood DNA for NQO1 Hinf I polymorphism was used in 311 unrelated Hindu individuals.

STATISTICAL ANALYSIS:

Allele frequencies were calculated by direct counting. Hardy Weinberg Equilibrium was evaluated using a Chi-square goodness of fit test.

RESULTS:

The observed allelic frequency was 81% for C (wild) and 19% for T (mutant) in the total sample.

CONCLUSIONS:

The allelic frequency of “C” was higher than in other Asians (57%), but similar to Caucasians (81%). The genotype distributions for Hinf I polymorphisms were in Hardy-Weinberg equilibrium.