Obstructive Lung Disease Study Research Articles

Comment on obstructive lung disease and obstructive sleep apnea (OLDOSA) cohort study: 10-year assessment

CITATIONHunasikatti M. Comment on obstructive lung disease and obstructive sleep apnea (OLDOSA) cohort study: 10-year assessment. J Clin Sleep Med. 2020;16(8):1389.

Prevalence and Characteristics of Undiagnosed COPD in Adults 40 Years and Older – Reports from the Tunisian Population-Based Burden of Obstructive Lung Disease Study

This study aimed to investigate the underdiagnosis of COPD and its determinants based on the Tunisian Burden of Obstructive Lung Disease study. We collected information on respiratory history symptoms and risk factors for COPD. Post-bronchodilator (Post-BD) FEV1/FVC < the lower limit of normal (LLN) was used to define COPD. Undiagnosed COPD was considered when participants had post-BD FEV1/FVC < LLN but were not given a diagnosis of emphysema, chronic bronchitis or COPD. 730 adults aged ⩾40 years selected from the general population were interviewed, 661 completed spirometry, 35 (5.3%) had COPD and 28 (80%) were undiagnosed with the highest prevalence in women (100%). When compared with patients with an established COPD diagnosis, undiagnosed subjects had a lower education level, milder airway obstruction (Post-BD FEV1 z-score −2.2 vs. −3.7, p < 0.001), fewer occurrence of wheezing (42.9% vs. 100%, p = 0.009), less previous lung function test (3.6% vs. 42.8%, p = 0.019) and less visits to the physician (32.1% vs. 85.7%, p = 0.020) in the past year. Multivaried analysis showed that the probability of COPD underdiagnosis was higher in subjects who had mild to moderate COPD and in those who did not visit a clinician and did not perform a spirometry in the last year. Collectively, our results highlight the need to improve the diagnosis of COPD in Tunisia. Wider use of spirometry should reduce the incidence of undiagnosed COPD. Spirometry should also predominately be performed not only in elderly male smokers but also in younger women in whom the prevalence of underdiagnosis is the highest.

Granularity of SERPINA1 alleles by DNA sequencing in CanCOLD.

DNA sequencing of the SERPINA1 gene to detect α1-antitrypsin (AAT) deficiency (AATD) may provide a better appreciation of the individual and cumulative impact of genetic variants on AAT serum levels and COPD phenotypes.AAT serum level and DNA sequencing of the coding regions of SERPINA1 were performed in 1359 participants of the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Clinical assessment for COPD included questionnaires, pulmonary function testing and computed tomography (CT) imaging. Phenotypes were tested for association with SERPINA1 genotypes collated into four groups: normal (MM), mild (MS and MI), intermediate (heterozygote MZ, non-S/non-Z/non-I, compound IS, and homozygote SS) and severe (ZZ and SZ) deficiency. Smoking strata and MZ-only analyses were also performed.34 genetic variants were identified including 25 missense mutations. Overall, 8.1% of alleles in this Canadian cohort were deficient and 15.5% of 1359 individuals were carriers of at least one deficient allele. Four AATD subjects were identified and had statistically lower diffusion capacity and greater CT-based emphysema. No COPD phenotypes were associated with mild and intermediate AATD in the overall cohort or stratified by smoking status. MZ heterozygotes had similar CT-based emphysema, but lowered diffusion capacity compared with normal and mild deficiency.In this Canadian population-based cohort, comprehensive genetic testing for AATD reveals a variety of deficient alleles affecting 15.5% of subjects. COPD phenotype was demonstrated in severe deficiency and MZ heterozygotes. This study shows the feasibility of implementing a diagnostic test for AATD using DNA sequencing in a large cohort.

Obstructive Lung Disease and Obstructive Sleep Apnea (OLDOSA) cohort study: 10-year assessment.

Asthma, chronic obstructive pulmonary disease (COPD), and obstructive sleep apnea (OSA) are very prevalent disorders. Their coexistence in the same individual has an unclear effect on natural history and long-term outcomes. The OLDOSA (Obstructive Lung Disease and Obstructive Sleep Apnea) cohort enrolled 4,980 veterans with an acute hospitalization and in whom asthma, COPD, OSA, overlapping conditions, or none of these disorders at baseline had been diagnosed. Pulmonary function, polysomnography, positive airway pressure (PAP) recommendations and adherence, and vital status were collected and analyzed. Various proportional hazards models were built for patients with OSA to test the effect of PAP therapy on survival. Ten-year all-cause cumulative mortality rate was 52.8%; median time to death was 2.7 years. In nonoverlapping asthma, OSA and COPD, mortality rates were 54.2%, 60.4%, and 63.0%, respectively. The overlap syndromes had the following mortality: COPD-OSA 53.2%, asthma-COPD 62.1%, asthma-OSA 63.5%, and triple overlap asthma-COPD-OSA 67.8%. In patients with OSA not on PAP therapy, after adjustment for age, comorbidities, and lung function, risk of death was 1.34 (1.05-1.71) times higher than those undergoing treatment. Similarly, in patients with OSA nonadherent to PAP therapy the adjusted risk of death was 1.78 (1.13-2.82) times higher versus those using it at least 70% of nights and more than 4 hours nightly. In this large longitudinal cohort of hospitalized veterans with high comorbid burden, asthma, COPD, OSA and their overlap syndromes had very high long-term mortality. In patients with OSA, PAP initiation and superior therapeutic adherence were associated with significantly better survival.

Sleep Quality and Nocturnal Symptoms in a Community-Based COPD Cohort

Small studies have suggested that patients with chronic obstructive pulmonary disease (COPD) have poor sleep quality. Our aim was to examine the prevalence of subjective sleep-related complaints and predictors of poor sleep quality in a large community-based COPD cohort. We analyzed cross-sectional data on sleep questionnaire responses from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study, a population-based, prospective longitudinal cohort study across Canada. The cohort comprises a COPD group and two matched non-COPD (never-smokers and ever-smokers) groups. Sleep-related symptoms were assessed using questionnaires including Pittsburgh Sleep Quality Index (PSQI). A total score of PSQI > 5 is indicative of poor sleep quality. Health-related quality of life measures and the presence of mood disturbance were assessed using Short Form-36™ Health Survey (SF-36) multi-item questionnaires and Hospital Anxiety and Depression Scale (HADS), respectively. Predictors of poor sleep quality were analyzed using multivariable logistic regression analysis. Of the 1123 subjects, 263 were healthy controls, 323 at-risk controls, and 537 had COPD (297 had mild, 240 with moderate to severe disease). The mean PSQI score was not significantly different between groups. COPD patients with poor sleep quality had lower diffusion capacity, higher HADS anxiety and depression scores and lower SF-36 mental and physical component summary scores than COPD patients classified as good sleepers. The presence of restless legs and obstructive sleep apnea symptoms, waist circumference, predicted diffusion capacity and HADS anxiety and depression scores were identified as independent predictors of poor sleep quality.

Mixed Phenotype of Emphysema and Airway Wall Thickening Is Associated with Frequent Exacerbation in Chronic Obstructive Pulmonary Disease Patients.

ObjectiveThe presence of both emphysema and airway wall thickening determined via volumetric computed tomography (CT) is defined as mixed phenotype. The long-term clinical course of this phenotype has not been studied in depth. This study compared the mixed phenotype to other phenotypes of chronic obstructive pulmonary disease (COPD) patients.MethodsCOPD patients enrolled in the Korean Obstructive Lung Disease (KOLD) study from June 2005 to October 2015 were evaluated. The emphysema index and the percentage of bronchial mean wall area were calculated from volumetric CT scans. Patients with COPD were classified into four phenotypes using two cutoffs: emphysema index of 15% and median value of mean wall area (MWA%).ResultsOf 435 patients with COPD, 99 (22.8%) were defined as CT-normal type, 119 (27.4%) as emphysema-dominant type, 113 (26.0%) as airway-dominant type, and 104 (23.9%) as mixed type. The mixed phenotype showed the highest baseline total COPD Assessment Test (CAT) and St. George’s Respiratory Questionnaire (SGRQ) scores. Moreover, it had the highest proportion of patients experiencing exacerbation of COPD (50.0%), and had the lowest baseline FEV1. Lower BMI, GOLD stages III–IV, and mixed phenotype were significant factors associated with severe exacerbation frequency in univariate analyses. Multivariate analyses showed that lower BMI and CT phenotype were significant factors associated with severe exacerbation frequency. Compared to the CT-normal phenotype, the mixed phenotype was significantly associated with more frequent severe exacerbation (IRR 4.134, 95% CI: 1.135–15.057, P=0.031).ConclusionPatients with mixed phenotype are more symptomatic, have poorer pulmonary function, and are associated with more frequent severe exacerbation.

Progression of erectile function in men with chronic obstructive pulmonary disease: a cohort study

BackgroundAlthough sexual function is a quality of life aspect that is markedly affected in males with chronic obstructive pulmonary disease (COPD), this topic has not attracted much attention and research on this matter is lacking. In this study, we investigated longitudinal changes in the erectile function of men with COPD in order to identify latent groups and influencing factors.MethodsA total of 185 men with COPD from the Korean Obstructive Lung Disease study, which was conducted from 2005 to 2013, were analyzed in this study. Data on their erectile function, based on the International Index of Erectile Function-5, were collected over a period of 4 years. Growth mixture modeling and logistic regression analysis were used to determine the factors predicting distinct erectile function changes over time.ResultsOverall, subjects’ erectile function slightly improved in the first year and then gradually worsened over time. Using growth mixture modeling, we identified four distinct latent groups, which we labeled as follows: “consistently maintained normal erectile function” (9.7%), “rapidly worsened and then rapidly improved” (9.2%), “gradually improved in the early stage and then gradually worsened” (36.8%), and “consistently maintained poor erectile function” (44.3%). Progression of erectile function was significantly associated with age, economic status, and self-rated health status.ConclusionsThis suggests that comprehensive patient care involving the management of COPD as well as erectile dysfunction in patients with chronic respiratory disease is important from a prophylactic perspective and should be developed in accordance with the characteristics of the disease process.

Impaired Sleep Quality in COPD Is Associated With Exacerbations: The CanCOLD Cohort Study

COPD increases susceptibility to sleep disturbances, which may in turn predispose to increased respiratory symptoms. The objective of this study was to evaluate, in a population-based sample, the relationship between subjective sleep quality and risk of COPD exacerbations. Data were obtained from the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Participants with COPD who had completed 18months of follow-up were included. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and a three-factor analysis. Symptom-based (dyspnea or sputum change ≥ 48 h) and event-based (symptoms plus medication or unscheduled health services use) exacerbations were assessed. Association of PSQI with exacerbation rate was assessed by using negative binomial regression. Exacerbation-free survival was also assessed. A total of 480 participants with COPD were studied, including 185 with one or more exacerbations during follow-up and 203 with poor baseline sleep quality (PSQI score > 5). Participants with subsequent symptom-based exacerbations had higher median baseline PSQI scores than those without (6.0 [interquartile range, 3.0-8.0] vs5.0 [interquartile range, 2.0-7.0]; P= .01), and they were more likely to have baseline PSQI scores > 5 (50.3%vs37.3%; P= .01). Higher PSQI scores were associated with increased symptom-based exacerbation risk (adjusted rate ratio, 1.09; 95%CI, 1.01-1.18; P= .02) and event-based exacerbation risk (adjusted rate ratio, 1.10; 95%CI, 1.00-1.21; P= .048). The association occurred mainly in those with undiagnosed COPD. Strongest associations were with Factor 3 (sleep disturbances and daytime dysfunction). Time to symptom-based exacerbation was shorter in participants with poor sleep quality (adjusted hazard ratio, 1.49; 95%CI, 1.09-2.03). Higher baseline PSQI scores were associated with increased risk of COPD exacerbation over 18months' prospective follow-up.

Genome-Wide Association Analysis of Single-Breath DlCO.

DlCO is a widely used pulmonary function test in clinical practice and a particularly useful measure for assessing patients with chronic obstructive pulmonary disease (COPD). We hypothesized that elucidating genetic determinants of DlCO could lead to better understanding of the genetic architecture of COPD. We estimated the heritability of DlCO using common genetic variants and performed genome-wide association analyses in four cohorts enriched for subjects with COPD (COPDGene [Genetic Epidemiology of COPD], NETT [National Emphysema Treatment Trial], GenKOLS [Genetics of Chronic Obstructive Lung Disease study], and TESRA [Treatment of Emphysema With a Gamma-Selective Retinoid Agonist study]) using a combined European ancestry white dataset and a COPDGene African American dataset. We assessed our genome-wide significant and suggestive associations for DlCO in previously reported genome-wide association studies of COPD and related traits. We also characterized associations of known COPD-associated variants and DlCO. We estimated the SNP-based heritability of DlCO in the European ancestry white population to be 22% (P = 0.0004). We identified three genome-wide significant associations with DlCO: variants near TGFB2, CHRNA3, and PDE11A loci (P < 5 × 10-8). In addition, 12 loci were suggestively associated with DlCO in European ancestry white (P < 1 × 10-5 in the combined analysis and P < 0.05 in both COPDGene and GenKOLS), including variants near NEGR1, CADM2, PCDH7, RETREG1, DACT2, NRG1, ANKRD18A, KRT86, NTN4, ARHGAP28, INSR, and PCBP3. Some DlCO-associated variants were also associated with COPD, emphysema, and/or spirometric values. Among 25 previously reported COPD loci, TGFB2, CHRNA3/CHRNA5, FAM13A, DSP, and CYP2A6 were associated with DlCO (P < 0.001). We identified several genetic loci that were significantly associated with DlCO and characterized effects of known COPD-associated loci on DlCO. These results could lead to better understanding of the heterogeneous nature of COPD.

Change in inhaled corticosteroid treatment and COPD exacerbations: an analysis of real-world data from the KOLD/KOCOSS cohorts

BackgroundThis cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines.MethodsA total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed. Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment. Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal.ResultsICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead. Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period. The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs. 0.53, p < 0.001). Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs. 0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs. 0.12, p = 0.03).ConclusionsPrescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators. ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients’ characteristics.

Reduced forced vital capacity is independently associated with ethnicity, metabolic factors and respiratory symptoms in a Caribbean population: a cross-sectional study

BackgroundRelationships between low forced vital capacity (FVC), and morbidity have previously been studied but there are no data available for the Caribbean population. This study assessed the association of low FVC with risk factors, health variables and socioeconomic status in a community-based study of the Trinidad and Tobago population.MethodsA cross-sectional survey was conducted using the Burden of Obstructive Lung Disease (BOLD) study protocol. Participants aged 40 years and above were selected using a two-stage stratified cluster sampling. Generalized linear models were used to examine associations between FVC and risk factors.ResultsAmong the 1104 participants studied a lower post-bronchodilator FVC was independently associated with a large waist circumference (− 172 ml; 95% CI, − 66 to − 278), Indo-Caribbean ethnicity (− 180 ml; 95% CI, − 90 to − 269) and being underweight (− 185 ml; 95% CI, − 40 to − 330). A higher FVC was associated with smoking cannabis (+ 155 ml; 95% CI, + 27 to + 282). Separate analyses to examine associations with health variables indicated that participants with diabetes (p = 0∙041), history of breathlessness (p = 0∙007), and wheeze in the past 12 months (p = 0∙040) also exhibited lower post-bronchodilator FVC.ConclusionThese findings suggest that low FVC in this Caribbean population is associated with ethnicity, low body mass index (BMI), large waist circumference, chronic respiratory symptoms, and diabetes.

A study of chronic obstructive lung disease among women

Background: Chronic obstructive pulmonary disease (COPD) is a preventable cause of globally occurring chronic illness. Although it is known to affect both men and women, there is a prevailing notion that it is essentially an illness of men. Hence, sufficient attention has not been given to COPD among women in our country. We undertook this study in this context. Aims and Objectives: We intended to study the clinical profile of COPD in women and the effect on biomass exposure on lung function. Materials and Methods: A total of 87 women with clinical and lung functional evidence of COPD were included. An enquiry was made to understand the risk factors for COPD. Biomass exposure index was calculated. Results: The severity of illness according to the Global Initiative for Chronic Obstructive Lung Disease staging revealed that 49.4% were in Grade 1 and 2 and 50.5% were in Grades 3 and 4. The duration of symptoms correlated with severity. Most patients were exposed to biomass smoke; the mean biomass index was 136.8 hour-years. The nature of exposure did not appear to influence the severity of illness. Conclusion: Multiple risk factors other than smoking also play a major role in development of COPD. Biomass exposure is a major risk factor in women and duration of exposure correlates with severity of the disease.

Burden of obstructive lung disease study in Iran: First report of the prevalence and risk factors of copd in five provinces.

Background:Chronic obstructive pulmonary disease (COPD) is a global health burden that affects 300 million people worldwide. Globally, COPD was reported as the fourth leading cause of death in 2004 and is projected to occupy the third position in 2030. The goal of the present project is to describe the prevalence and determine the causes and risk factors of COPD in five provinces of Iran.Methods:This study followed a stratified cluster sampling strategy with proportional allocation within strata. The target population is all noninstitutionalized inhabitants, aged 18 and over, who inhabit in different provinces in Iran in the year 2017. The stratification of the sample according to the 31 provinces of Iran is incorporated in the sampling process. The core questionnaire was developed from preexisting validated questionnaires. The single most important outcome measure obtained as part of this protocol was spirometry before and after the administration of 200 mg (two puffs) of salbutamol.Results:The most commonly reported respiratory symptoms were as follows: wheezing (N=217, 20.4%, 95% confidence interval [CI]: 18%–22.8%), sputum production (N=173, 16.5%, 95% CI: 14.3%–18.8%), and dyspnea (N=131, 12.3%, 95% CI: 10.3%–14.3%). The overall COPD prevalence defined by the postbronchodilator spirometric Global Initiative for Chronic Obstructive Lung Disease criteria was 4.9%, higher in men (6.4%) than in women (3.9%). The prevalence of COPD was strongly dependent on smoking status, age, and sex.Conclusion:COPD is considered a preventable disease, and avoidance of exposure to major risk factors can prevent the vast majority of cases. The present study findings add to the literature on the prevalence of COPD in Iran and will help policy-makers, specialists, and all stakeholders to strategize and evaluate medical services required for reducing the prevalence of respiratory diseases. The data from our present study will serve as baseline information for future national and regional studies of COPD.

Improvement of fully automated airway segmentation on volumetric computed tomographic images using a 2.5 dimensional convolutional neural net.

We propose a novel airway segmentation method in volumetric chest computed tomography (CT) and evaluate its performance on multiple datasets. The segmentation is performed voxel-by-voxel by a 2.5D convolutional neural net (2.5D CNN) trained in a supervised manner. To enhance the accuracy of the segmented airway tree, we simultaneously took three adjacent slices in each of the orthogonal directions including axial, sagittal, and coronal and fine-tuned the parameters that influence the tree length and the number of leakage. The gold standard of airway segmentation was generated by a semi-automated method using AVIEW™. The 2.5D CNN was trained and evaluated on a subset of inspiratory thoracic CT scans taken from the Korean obstructive lung disease study, which includes normal subjects and chronic obstructive pulmonary disease patients. The reliability and further practicality of our proposed method was demonstrated in multiple datasets. In eight test datasets collected by the same imaging protocol, the percentage detected tree length, false positive rate, and Dice similarity coefficient of our method were 92.16%, 7.74%, and 0.8997 ± 0.0892, respectively. In 20 test datasets of the EXACT'09 challenge, the percentage detected tree length was 60.1% and the false positive rate was 4.56%. Our fully automated (end-to-end) segmentation method could be applied in radiologic practice.

The impact of 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines on allocation and pharmacological management of patients with COPD in Taiwan: Taiwan Obstructive Lung Disease (TOLD) study.

BackgroundThis nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.Subjects and methodsData were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.ResultsA total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.ConclusionThe distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients.

Accuracy of diagnosis of COPD and factors associated with misdiagnosis in primary care setting. E-DIAL (Early DIAgnosis of obstructive lung disease) study group.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and results in both substantial and increasing socioeconomic burden. Guidelines on COPD encourage primary care physicians to detect the disease at an early stage. Our main aim was to evaluate the accuracy of the diagnosis of COPD at the primary health care. 6466 patients were randomly selected in 22 Italian primary care practices (46% males, mean age 56 ± 16 years) and were asked about respiratory symptoms and risk for any chronic respiratory disease including COPD. After a prior evaluation, 701 patients (51% males, mean age 59 ± 15 years) were sent by General Practitioners (GPs) to Pulmonary Units (PU) for confirming the diagnosis. The agreement in diagnosing COPD between GPs and pulmonary diseases specialists was assessed by using Cohen's kappa (k) statistic. Lack of precision in COPD diagnosis resulted in 13% of over-diagnosis and 59% of under-diagnosis. GPs were quite good in correctly excluding the patients who did not have COPD (specificity = 87%), but less good in diagnosing the patients with COPD (sensitivity = 41%). The risk of under-diagnosis was higher in people with age >62 years and in current/ex-smokers, when compared to no COPD, whereas it was higher in subject <62 years old and in those with no previous spirometry when compared to correctly diagnosed COPD. Our results confirm that COPD misdiagnosis is common in primary care and that under-diagnosis is a major problem. It is necessary to enhance COPD diagnosis and to reduce misdiagnosis in primary care settings.

Association of Elevated Serum GM-CSF, IFN-γ, IL-4, and TNF-α Concentration with Tobacco Smoke Induced Chronic Obstructive Pulmonary Disease in a South Indian Population.

Background Chronic obstructive pulmonary disease (COPD) is a devastating condition with limited pharmacotherapeutic options and exceptionally high public-health burden globally as well as in India. Tobacco smoking is the primary cause for COPD among men in India. Systemic inflammation involving altered regulation of cytokines controlling the host defense mechanism is a hallmark of COPD pathogenesis. However, biomarker discovery studies are limited among Indian COPD patients. Methods We assessed the serum concentrations [median (25th-75th percentile) pg/ml] of interleukin (IL)-2,4,6,8,10, granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) using a multiplexed immunoassay. Our study cohort consisted of 30 tobacco smokers with COPD (TS COPD) and 20 tobacco smokers without COPD (TS CONTROL) from South India. The study population was matched for age, sex (male), and tobacco consumption (pack-years). COPD was diagnosed according to the global initiative for chronic obstructive lung disease (GOLD) criteria of persistent airflow obstruction determined by the ratio of postbronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of <0.7. A validated structured questionnaire-based survey [Burden of Obstructive Lung Disease (BOLD) study] and spirometry were performed during house to house visit of the field study. Statistical analysis included nonparametric (two-tailed) Mann–Whitney U and Spearman rank test, as appropriate (significance: p<0.05). Results Serum GM-CSF [69.64 (46.67, 97.48); 36.78 (30.07, 53.88), p=0.014], IFN-γ [51.06 (17.00, 84.86); 11.70 (3.18, 32.81), p=0.017], IL-4 [9.09 (1.8, 19.9); 1.8 (1.8, 4.46); p=0.024], and TNF-α [20.68 (5.5, 29.26); 3.5 (3.5, 4.5); p<0.001] concentrations (pg/ml) were increased in TS COPD subjects compared to TS CONTROL. A weak correlation between lung function parameters and cytokine concentrations was detected. Conclusion Our pilot study reveals GM-CSF, IFN-γ, IL-4, and TNF-α as plausible COPD susceptibility biomarkers within the investigated South Indian population that needs to be validated in a larger cohort.

Alternative definitions of chronic bronchitis and their correlation with CT parameters.

IntroductionPhenotyping of chronic bronchitis (CB) using COPD assessment tool (CAT) scores and St George’s Respiratory Questionnaire (SGRQ) has rarely been attempted. The present study defined CB using CAT 1 and 2 scores and the questions on the severity of cough and sputum from the SGRQ. Furthermore, the predictability of CT parameters was also assessed for each CB definition.Materials and methodsPatients enrolled in the Korean Obstructive Lung Disease study from June 2005 to October 2015 were evaluated for this study. The patients were spirometrically diagnosed with COPD and had a smoking history of >10 pack-years. Volumetric CT scans were performed for each patient upon enrollment in the cohort. Two definitions of CB using CAT 1/2 scores and SGRQ questions were used to phenotype CB among the study patients. Receiver operating characteristic curve analysis was performed to estimate the predictability of CT parameters for the CB phenotypes.ResultsUsing CAT 1/2 scores, 57 of 279 (20.4%) patients had CB, and 178 of 573 (31.1%) had CB when the SGRQ questions were used to phenotype it. Total CAT and SGRQ scores were significantly higher in the CB group than those in the non-CB group for both definitions of CB. Forced expiratory volume in 1 second was lower for both CAT-defined and SGRQ-defined CB than that in the non-CB group. Mean wall thickness was significantly higher for both CB groups than in the non-CB group. Expiratory lung volume was higher and mean lung density was significantly lower for the SGRQ-defined CB group than non-CB group.ConclusionThe 2 CB definitions using CAT scores and the SGRQ questions correlated with associated CT airway parameters. SGRQ-defined CB better reflected the accompaniment of small airway obstruction when compared with CAT-defined CB.

Predictive value of eosinophils and neutrophils on clinical effects of ICS in COPD.

Inflammation is present to a variable degree and composition in patients with COPD. This study investigates associations between both eosinophils and neutrophils in blood, sputum, airway wall biopsies and bronchoalveolar lavage (BAL) and their potential use as biomarkers for clinical response to inhaled corticosteroids (ICS). In total, 114 steroid-naïve COPD patients of the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study using ICS or placebo during 30-month follow-up were included. Cell counts in blood, sputum, biopsies and BAL were evaluated at baseline. In addition, at baseline, 6 and 30 months, forced expiratory flow in 1 s (FEV1 ), residual volume/total lung capacity (hyperinflation) and Clinical COPD Questionnaire were evaluated. Cross-sectional analyses at baseline showed that higher blood eosinophils were significantly associated with higher eosinophil counts in sputum, biopsies and BAL. However, blood neutrophils did not significantly correlate with neutrophil counts in the other compartments. Baseline eosinophils and neutrophils, in whichever compartment measured, did not predict longitudinal FEV1 changes. Higher baseline biopsy eosinophils were associated with an increase in symptoms during 6- and 30-month ICS treatment. In addition, higher biopsy neutrophils were associated with a more marked reduction in hyperinflation during 6-month ICS treatment compared with placebo. Our findings indicate that blood eosinophils reflect eosinophils in other compartments, in contrast to neutrophils, in ICS-naïve COPD patients. Both baseline eosinophils and neutrophils do not predict ICS-induced lung function changes over a period of 6-30 months. The associations of biopsy eosinophils with worsening respiratory symptoms and biopsy neutrophils with improvement in hyperinflation during ICS treatment deserve further investigation.

Health Services Burden of Undiagnosed and Overdiagnosed COPD

Misdiagnosis of COPD is common. The goal of this study was to quantify the health services burden of undiagnosed and overdiagnosed COPD in a real-world, North American population. A population-based cohort study was conducted. Presence of COPD using spirometry was ascertained in randomly selected adults aged≥ 40 years from Ontario, Canada, who participated in the Canadian Obstructive Lung Disease study. The presence of physician-diagnosed COPD was ascertained for the same subjects by using linked health administrative data. Participants were then categorized into four groups: correctly diagnosed, undiagnosed, overdiagnosed, and no COPD according to either criteria. Age- and sex-standardized rates of hospitalizations, ED visits, and ambulatory care visits in each group were determined and compared. Of 1,403 participants, 13.7%had undiagnosed COPD, 5.1%were overdiagnosed, and 3.7%had correctly diagnosed COPD. Subjects with overdiagnosed COPD had significantly higher rates of hospitalizations, ED visits, and ambulatory care visits, and subjects with moderate to severe undiagnosed COPD had higher rates of hospitalizations, than subjects in the non-COPD population. Undiagnosed and overdiagnosed COPD contribute to significant health care burden. Given that misdiagnosed COPD was fivefold more common than correctly diagnosed COPD, these findings point to a substantial misdiagnosis-associated burden of disease that might be prevented, at least in part, with a correct diagnosis.