Chronic Obstructive Lung Disease Stage Research Articles

Abstract TP357: Risk Factors of Stroke Among Community- residing Patients with Chronic Obstructive Pulmonary Disease (copd)

Introduction: Worldwide, chronic obstructive pulmonary disease (COPD) and stroke are leading causes of death. Increasing evidence suggests that COPD patients have a higher risk of stroke than the general population Objectives: This study was undertaken to investigate risk factors of stroke including concurrent cardiovascular disease(CVD); to explore differences of these variables and their relationships according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage among community-residing patients with COPD. Methods: A total of 118 participants with mean aged 69.4 years old were recruited among those patients with COPD who have been treated at the outpatient department of pulmonology at a University hospital in an urban area of South Korea. Along with BP and anthropometric measurement, trained interviewers interviewed participants with a structured questionnaire including demographic characteristics, lifestyle risk factors, and comorbid CVD. Data were analyzed using SPSS statistics 20.0 Results: Most of participants (89.8%) were men, almost half (50.4%) of them were categorized into GOLD stage II, and 39.3 % and 10.3 % of them were GOLD stage III and IV, respectively. Mean systolic BP of participants was 123.8 mmHg and mean diastolic BP, 80.3 mmHg. Seventy percent of them were currently non-smoker and 45% of them did not drink. Sixty eight percent of them had no CVD, while 32% of them had been diagnosed with and treated due to hypertension, atrial fibrillation, or coronary artery diseases. The duration of COPD diagnosis was significantly shorter among those who had comorbid CVD. There were no significant differences in histories of smoking or drinking according to the GOLD stages. However, those in GOLD stage II had more CVD than those in COLD stage III and IV. Also, age and BMI showed significant differences according to the GOLD stages. Conclusions: The findings demonstrated the presences of stroke risk factors and possible associations between some risk factors, such as comorbid CVD, and COPD severity among patients with COPD. Further research is needed to explore the precise relationships among stroke risk, concurrent CVD, and the severity, duration, treatment of exacerbations of COPD among this population.

The relationship between metabolic syndrome and chronic obstructive pulmonary disease

BackgroundMetabolic syndrome is a condition frequently found among individuals. It predisposes affected individuals to systemic inflammation and physical inactivity. The aim of the present study was to investigate the frequency of metabolic syndrome and C-reactive protein (CRP) levels as markers of systemic inflammation in stable chronic obstructive pulmonary disease (COPD) patients with different severity levels and in an age-matched and sex-matched control group.Patients and methodsOne hundred COPD patients and 50 controls were included in this study. The severity level in patients with COPD was determined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I−IV, we measured the characteristics of the metabolic syndrome and systemic inflammation (high-sensitivity Creactive protein).ResultsThe frequency of metabolic syndrome was found to be higher in the patient group than in control individuals, especially in GOLD stages I and II. Abdominal obesity, hypertension, and hyperglycemia components of metabolic syndrome were significantly more prevalent in the patient group (P<0.05 for all). Increased CRP levels were higher in control and patient groups in all GOLD stages, with metabolic syndrome than without metabolic syndrome. P-values for control group and GOLD stages I–IV were 0.044, 0.483, less than 0.01, 0.048, and 0.076, respectively.ConclusionMetabolic syndrome is substantial among stable COPD patients, especially in the early stages (GOLD stages I−II). Abdominal obesity, hypertension, and hyperglycemia were significantly more in COPD patients with metabolic syndrome. An impaired profile of CRP levels was found in patients and control groups with metabolic syndrome than in individuals without metabolic syndrome.

Two-year mortality in survivors of acute exacerbations of chronic obstructive pulmonary disease: A North Indian study.

Objectives:Data about long-term mortality of Indian patients following acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are scant. We set out to study the 2-year mortality in north Indian patients following discharge after AECOPD.Materials and Methods:One hundred and fifty-one (96 male) patients admitted for AECOPD and discharged were followed for 2 years at 3, 6, 12, 18, and 24 months for mortality. Statistical analysis was performed to identify risk factors associated with mortality.Results:Sixty (39.7%) of the 151 recruited died during the 24 months of follow-up, 30 (19.8%) at 3-month, 43 (28.5%) at 6-month, 49 (32.4%) at 1-year, 55 (36.4%) at 18-month, and 60 (39.7%) at 2 years. There was no mortality in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Stage I (0 of 6 cases), whereas it was 12.3% (n = 8 of 65 patients) in GOLD Stage II, 41.7% (n = 15 of 36 cases), in GOLD Stage III, and 84.1% (n = 37 of 4 cases), of patients with GOLD Stage IV. Mortality was associated with 6-min walk distance, oxygen saturation, low body mass index, history of congestive heart failure, and St. George Respiratory Questionnaire score.Conclusion:Indian patients discharged after AECOPD have a high 2-year mortality. Measures to reduce the frequency of exacerbations need to be routinely adopted in patients with COPD.

The Correlation of Serum Brain Natriuretic Peptide and Interleukin-6 with Quality of Life Using the Chronic Obstructive Pulmonary Disease Assessment Test

Objective: The aim of this study was to determine the levels of serum pro-brain natriuretic peptide (pro-BNP) and interleukin (IL)-6 in patients with stable chronic obstructive pulmonary disease (COPD) and to correlate these markers with health-related quality of life using the COPD assessment test (CAT). Materials and Methods: Serum pro-BNP and IL-6 levels were measured in 82 patients with stable COPD. Serum pro-BNP and serum IL-6 levels, pulmonary function, and oxygen saturation (SpO₂) were measured according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and CAT score. Also, the associations of both pro-BNP and IL-6 with the clinical parameters of patients were tested. Results: The serum levels of IL-6 (7.57 [5-11.16] pg/mL) and pro-BNP (120.55 [92.89-144.20] pg/mL) were higher with enhancing disease severity based on the GOLD classification (p = 0.034 and 0.068, respectively). Also, serum levels of pro-BNP (120.55 [89.50-147.90] pg/mL) and IL-6 (6.68 [4.40-11.97] pg/mL) were increased in patients with high CAT scores (p = 0.004 and 0.017, respectively). There was a significant positive correlation between plasma pro-BNP and IL-6 levels (r = 0.332, p = 0.002). Conclusion: The results demonstrated that with increased severity of obstruction based on the GOLD criteria both IL-6 and pro-BNP were elevated. This increase in inflammatory markers was associated with a reduced quality of life and the severity of hypoxia. These findings indicated that lowering IL-6 and pro-BNP could be useful in the management of COPD patients.

Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD

ABSTRACTThere is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation (E)/CO2 output (CO2) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake (O2), higher E/CO2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak O2 and worse dyspnea were found in patients with higher E/CO2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-O2 exercise (p < 0.05). Higher E/CO2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = −0.72) and blunted changes in PBF from rest to exercise (r = −0.69) (p < 0.01). Ventilation “wasted” in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (DLCO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

Instability of Willingness to Accept Life-Sustaining Treatments in Patients With Advanced Chronic Organ Failure During 1 Year

For optimal end-of-life decision-making, it is important to understand the stability of patients' treatment preferences. The aim of this paper is to examine the stability of willingness to accept life-sustaining treatments during 1-year follow-up in Dutch patients with advanced chronic organ failure. In addition, we want to explore the association between willingness to accept high-burden treatment and preferences for CPR and mechanical ventilation (MV). In this multicenter longitudinal study, 265 clinically stable outpatients with advanced COPD (Global Initiative for Chronic Obstructive Lung Disease stage III/IV [n=105]), chronic heart failure (New York Heart Association class III/IV [n= 80]), or chronic renal failure (requiring dialysis [n= 80) were visited at baseline and at 4, 8, and12months to assess the stability of life-sustaining treatment preferences using the Willingness to Accept Life-sustaining Treatment instrument. Two hundred six patients completed 1-year follow-up (mean age, 67.2 years [SD, 13.1 years]; 64.1%men). Overall, proportions of patients who were willing to accept life-sustaining treatment during 1 year did not change over time. However, individual trajectories showed that about two-thirds of patients changed their preferences at least once during a year. Moreover, there was no association found between the stability of willingness to undergo high-burden therapy and the stability of preferences for CPR and MV. The current findings show the complexity of preferences for end-of-life care and indicate once again that advance care planning is a continuous process between patients and physicians, in which preferences for specific situations are discussed and that needs to be regularly reevaluated to deliver high-quality end-of-life care. Netherlands National Trial Register (NTR 1552).

Tuberculosis, Airway Obstruction and Mortality in a Finnish Population

ABSTRACTThere is little long-term follow-up data concerning the association between past pulmonary tuberculosis (TB), airway obstruction and mortality. We aimed to analyse a national health examination survey data from 6701 adult Finns undergoing spirometry between 1978 and 1980 (follow-up through 2013). We identified TB either through a disease history or by a TB-indicative scar on a chest x-ray. We specified obstruction using the lower limit of normal (LLN) and classified severity using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1–4. After adjusting for smoking and other confounders, past TB associated with obstruction. Compared to non-TB patients, the adjusted odds ratio (OR; 95% CI) of obstruction reached 2.21 (1.52–3.21) among patients with a scar recorded by one radiologist, 2.48 (1.63–3.78) when recorded by both radiologists and 4.59 (2.86–7.37) among patients with a disease history. Among those with neither past TB nor obstruction, with past TB only, with an obstruction only and with both, we found hazard ratios (HRs; 95% CIs) for subsequent mortality of 1.00 (reference), 1.11 (1.03–1.20), 1.62 (1.31–2.00) and 1.77 (1.45–2.16), adjusted for age, gender, smoking, body mass index (BMI), physical activity, education and general health. In conclusion, past TB strongly determines obstruction, although on its own quite weakly predicts premature death. TB and obstruction combined predict an additive mortality pattern.

The burden of chronic obstructive pulmonary disease associated with maintenance monotherapy in the UK.

BackgroundThis study characterized a cohort of chronic obstructive pulmonary disease (COPD) patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization.MethodsData were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β2-adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013) or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients’ rate of face-to-face interactions with a health care professional (HCP), COPD-related exacerbations, hospitalizations, and referrals.ResultsA cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B) on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on maintenance bronchodilator monotherapy was 2 years. The median number of prescriptions was 14. On average, patients had 15 HCP interactions per year, and one in ten patients experienced a COPD exacerbation (N=8,811). One in 50 patients were hospitalized for COPD per year (n=4,848).ConclusionThe average monotherapy-treated patient had a higher than average HCP interaction rate. We also identified a large cohort of patients who were stepped up to triple therapy despite a low rate of exacerbations. The use of the new class of long-acting muscarinic antagonist/long-acting β2-adrenergic agonist fixed-dose combinations may provide a useful step-up treatment option in such monotherapy patients, before the use of inhaled corticosteroids.

Chronic Obstructive Pulmonary Disease: Lobar Analysis with Hyperpolarized 129Xe MR Imaging.

Purpose To compare lobar ventilation and apparent diffusion coefficient (ADC) values obtained with hyperpolarized xenon 129 (129Xe) magnetic resonance (MR) imaging to quantitative computed tomography (CT) metrics on a lobar basis and pulmonary function test (PFT) results on a whole-lung basis in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods The study was approved by the National Research Ethics Service Committee; written informed consent was obtained from all patients. Twenty-two patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent hyperpolarized 129Xe MR imaging at 1.5 T, quantitative CT, and PFTs. Whole-lung and lobar 129Xe MR imaging parameters were obtained by using automated segmentation of multisection hyperpolarized 129Xe MR ventilation images and hyperpolarized 129Xe MR diffusion-weighted images after coregistration to CT scans. Whole-lung and lobar quantitative CT-derived metrics for emphysema and bronchial wall thickness were calculated. Pearson correlation coefficients were used to evaluate the relationship between imaging measures and PFT results. Results Percentage ventilated volume and average ADC at lobar 129Xe MR imaging showed correlation with percentage emphysema at lobar quantitative CT (r = -0.32, P < .001 and r = 0.75, P < .0001, respectively). The average ADC at whole-lung 129Xe MR imaging showed moderate correlation with PFT results (percentage predicted transfer factor of the lung for carbon monoxide [Tlco]: r = -0.61, P < .005) and percentage predicted functional residual capacity (r = 0.47, P < .05). Whole-lung quantitative CT percentage emphysema also showed statistically significant correlation with percentage predicted Tlco (r = -0.65, P < .005). Conclusion Lobar ventilation and ADC values obtained from hyperpolarized 129Xe MR imaging demonstrated correlation with quantitative CT percentage emphysema on a lobar basis and with PFT results on a whole-lung basis. © RSNA, 2016.

Chronotropic incompetence can limit exercise tolerance in COPD patients with lung hyperinflation.

PurposeMetabolic-chronotropic relationship is the only concept that assesses the entire chronotropic function during exercise, as it takes into account individual fitness. To better understand interrelationships between chronotropic incompetence (CI), dynamic hyperinflation (DH) and exercise limitation among Global initiative for chronic Obstructive Lung Disease (GOLD) stages of chronic obstructive pulmonary disease (COPD) disease severity, we evaluated cardiopulmonary responses to symptom-limited cycle exercise in stable patients.Patients and methodsWe prospectively studied 47 COPD patients classified by GOLD stage severity. Pulmonary function tests and cardiopulmonary responses to symptom-limited incremental exercise were studied. CI was defined by regression line between percent heart rate (HR) reserve and percent oxygen uptake (V’O2) reserve, ie, chronotropic-metabolic index (CMI). DH was defined from the knot resulting from the nonlinear regressions of inspiratory capacity changes from rest to peak (dynamic inspiratory capacity (ICdyn)) with percentage of maximal HR and CMI.ResultsAerobic capacity (median interquartile ranges) peak V’O2, 24.3 (23.6; 25.2), 18.5 (15.5; 21.8), 17.5 (15.4; 19.1) mL·kg−1·min−1 and CMI worsened according to GOLD severity. The optimal knot of ICdyn was equal to −0.34 L. The multivariate logistic regression showed a strong relationship between CI (outcome) and DH (odds ratio [confidence interval 95]) 25 (3.5; 191.6).ConclusionCOPD patients with DH have a poor cardiovascular response to exercise, which may be attributed to CI.

Contractile capability of the diaphragm assessed by ultrasonography predicts nocturnal oxygen saturation in COPD.

Diaphragm function might be useful to predict nocturnal oxygen desaturation in COPD. Ultrasonography has been widely used for the assessment of the diaphragm. We aimed to investigate the relationship between the contractile capability of the diaphragm assessed by ultrasonography and the nocturnal percutaneous arterial oxygen saturation (NSpO2 ) in COPD. Twenty-eight male patients with COPD (age, 73 ± 7 years; forced expiratory volume in 1 s (FEV1 ), 54.2 ± 17.0% predicted) were included. The thickness of the diaphragm (Tdi) was assessed by ultrasonography. We calculated the change ratio of Tdi at the end of maximal inspiration and expiration (%ΔTdi). The mean value of NSpO2 (NSpO2mean ), the percentage of total sleep time (TST) with desaturation above 4% (DA4%) and the percentage of TST with saturation below 90% (SB90%) were measured by overnight oximetry. Daytime arterial oxygen pressure (PaO2 ) and maximal inspiratory mouth pressure (PImax ) were also measured. All participants had mild or no daytime hypoxaemia (PaO2 , 77.3 ± 8.6 mm Hg). The NSpO2mean , DA4% and SB90% were significantly correlated with %ΔTdi, PaO2 , %PImax of the predicted value and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The %ΔTdi and PaO2 were predictors of NSpO2 mean by multiple regression analysis. This study suggested a close relationship between the NSpO2 and the contractile capability of the diaphragm assessed by ultrasonography in COPD. The %ΔTdi combined with PaO2 might predict NSpO2 in COPD patients with mild or no daytime hypoxaemia.

Respiratory and Bronchitic Symptoms Predict Intention to Quit Smoking among Current Smokers with, and at Risk for, Chronic Obstructive Pulmonary Disease.

Smoking cessation is the most important intervention for patients with chronic obstructive pulmonary disease (COPD). What leads smokers with COPD to quit smoking remains unknown. We sought to examine the association between respiratory symptoms and other markers of COPD severity with intention to quit smoking among a cohort of patients with probable COPD. We conducted a cross-sectional study of subjects with COPD or fixed airflow obstruction clinically diagnosed on the basis of pulmonary function testing. The subjects were identified in the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation multicenter registry. The primary outcome was the intention to quit smoking within the next 30 days (yes or no), which was examined using model building with multivariable logistic regression, clustered by study site. We identified 338 current smokers with COPD via the registry. Of these subjects, 57.4% (n = 194) had confirmed airflow obstruction based on pulmonary function testing. Nearly one-third (29.2%; n = 99) intended to quit smoking in the next 30 days. In adjusted analyses, compared with subjects without airflow obstruction based on pulmonary function testing, subjects with Global Initiative for Chronic Obstructive Lung Disease stage I/II COPD were more likely to be motivated to quit (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.37-2.49), with no association found for subjects with Global Initiative for Chronic Obstructive Lung Disease stage III/IV disease. Among the entire cohort, frequent phlegm (OR, 2.10; 95% CI, 1.22-3.64), cough (OR, 1.74; 95% CI, 1.01-2.99), wheeze (OR, 1.73; 95% CI, 1.09-3.18), and higher modified Medical Research Council dyspnea score (OR, 1.26 per point; 95% CI, 1.13-1.41) were associated with increased odds of intending to quit smoking. Low self-reported health was associated with decreased odds of intending to quit (OR, 0.75; 95% CI, 0.62-0.92). Frequent cough, phlegm, wheeze, and shortness of breath were associated with intention to quit smoking in the next 30 days, with a less clear relationship for severity of illness graded by pulmonary function testing and self-rated health. These findings can be used to inform the content of tobacco cessation interventions to provide a more tailored approach for patients with respiratory diseases such as COPD.

Speckle tracking echocardiography in chronic obstructive pulmonary disease and overlapping obstructive sleep apnea.

BackgroundCOPD and congestive heart failure represent two disease entities of growing global burden that share common etiological features. Therefore, we aimed to identify the degree of left ventricular (LV) dysfunction in COPD as a function of COPD severity stages and concurrently placed particular emphasis on the presence of overlapping obstructive sleep apnea (OSA).MethodsA total of 85 COPD outpatients (64.1±10.4 years, 54.1% males) and 20 controls, matched for age, sex, and smoking habits, underwent speckle tracking echocardiography for LV longitudinal strain imaging. Complementary 12-lead electrocardiography, laboratory testing, and overnight screening for sleep-disordered breathing using the SOMNOcheck micro® device were performed.ResultsContrary to conventional echocardiographic parameters, speckle tracking echocardiography revealed significant impairment in global LV strain among COPD patients compared to control smokers (−13.3%±5.4% vs −17.1%±1.8%, P=0.04). On a regional level, the apical septal LV strain was reduced in COPD (P=0.003) and associated with the degree of COPD severity (P=0.02). With regard to electrocardiographic findings, COPD patients exhibited a significantly higher mean heart rate than controls (71.4±13.0 beats per minute vs 60.3±7.7 beats per minute, P=0.001) that additionally increased over Global Initiative for Chronic Obstructive Lung Disease stages (P=0.01). Albeit not statistically significant, COPD led to elevated N-terminal pro-brain natriuretic peptide levels (453.2±909.0 pg/mL vs 96.8±70.0 pg/mL, P=0.08). As to somnological testing, the portion of COPD patients exhibiting overlapping OSA accounted for 5.9% and did not significantly vary either in comparison to controls (P=0.07) or throughout the COPD Global Initiative for Chronic Obstructive Lung Disease stages (P=0.49). COPD-OSA overlap solely correlated with nocturnal hypoxemic events, whereas LV performance status was unrelated to coexisting OSA.ConclusionTo conclude, COPD itself seems to be accompanied with decreased LV deformation properties that worsen over COPD severity stages, but do not vary in case of overlapping OSA.

Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study

BackgroundFrailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people. The relevance of frailty to chronic respiratory disease and its management is unknown.ObjectivesTo determine...

Chronic bronchitis is an independently associated factor for more symptom and high-risk groups.

BackgroundThe chronic bronchitis (CB) phenotype has been associated with poor quality of life and an increased risk of disease in patients with COPD. However, little information exists regarding the relationship between the CB phenotype and the COPD assessment test (CAT) score. The goal of this study was to reveal the different pattern of CAT scores between CB and non-CB patients. Moreover, we aimed to investigate whether the CB phenotype is an independently associated factor for more symptom and high-risk groups.MethodsData were obtained from the Korea COPD Subgroup Study cohort recruited from 46 centers in South Korea since April 2012. CB patients were defined as having a chronic cough and sputum for 3 months per year, for a period of 2 consecutive years. We investigated the pattern of CAT and subquestionnaire scores between CB and non-CB patients. We also analyzed the proportion of CB phenotypes in each Global initiative for chronic Obstructive Lung Disease (GOLD) stage. Finally, we performed a logistic regression analysis to identify whether the CB phenotype was an independently associated factor for more symptom and high-risk groups.ResultsOf the 1,106 study patients, 11.5% of patients were found to have a CB phenotype. CB phenotypes were most common in GOLD III (GOLD 2006) and GOLD D (GOLD 2015) stages. CAT scores were significantly higher in CB patients not only in terms of the total score but also for each subquestionnaire. Logistic regression revealed that the CB phenotype is an independently associated factor for more symptom and high-risk groups.ConclusionThe present study revealed that CB patients have higher CAT scores and subquestionnaire results compared to non-CB patients. Additionally, we demonstrated that the CB phenotype is an independently associated factor for both more symptom and high-risk groups.

Epidemiology and survival of idiopathic pulmonary fibrosis from national data in Canada.

Idiopathic pulmonary fibrosis (IPF) is a rare disease, with estimates of prevalence varying considerably across countries due to paucity in data collection. The aim of this study was to investigate the prevalence and incidence of IPF in Canada using administrative data requiring minimal extrapolation.We used mandatory national administrative data from 2007-2011 to identify IPF cases of all ages with an International Classification of Diseases (Version 10, Canadian) diagnosis code of J84.1. We used a broad definition that excluded cases with subsequent diagnosis of other interstitial lung diseases, and a narrow definition that required further diagnostic testing prior to IPF diagnosis. We explored survival and quality of life.For all ages, the broad prevalence of IPF was 41.8 per 100 000 (14 259 cases) and was higher for men. The incidence rate was 18.7 per 100 000 (6390 cases) and was higher for men. The narrow prevalence was 20.0 per 100 000 (6822 cases) and incidence was 9.0 per 100 000 (3057 cases). The 4-year risk of death was 41.0% and the quality of life with IPF after 2 years was lower than for Global Initiative for Chronic Obstructive Lung Disease stage IV chronic obstructive pulmonary disease.Using comprehensive national data, the prevalence of IPF in Canada was higher than other national estimates, suggesting that either IPF may be more common in Canada or that data capture may have been previously limited.

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.

Are interstitial lung abnormalities associated with COPD? A nested case-control study.

PurposeIn this study, we tested the association between COPD and interstitial lung abnormality (ILA), notably in relation to the presence of computed tomography (CT) signs of lung fibrosis.Patients and methodsCOPD cases were selected from participants undergoing lung cancer screening (Multicentric Italian Lung Detection trial) for airflow obstruction (n=311/2,303, 13.5%) and 146 consecutive patients with clinical COPD. In all, 457 COPD cases were selected and classified according to the stages of Global Initiative for Chronic Obstructive Lung Disease. A nested matching (case:control = 1:2) according to age, sex, and smoking history was operated between each COPD case and two control subjects from Multicentric Italian Lung Detection trial without airflow obstruction. Low-dose CT scans of COPD cases and controls were reviewed for the presence of ILA, which were classified into definite or indeterminate according to the presence of signs of lung fibrosis.ResultsThe frequency of definite ILA was similar between COPD cases and controls (P=0.2), independent of the presence of signs of lung fibrosis (P=0.07). Combined definite and indeterminate ILA was homogeneously distributed across Global Initiative for Chronic Obstructive Lung Disease stages (P=0.6). Definite ILA was directly associated with current smoker status (odds ratio [OR] 4.05, 95% confidence interval [CI]: 2.2–7.4) and increasing pack-years (OR 1.01, 95% CI: 1–1.02). Subjects with any fibrotic ILA were more likely to be older (OR 1.17, 95% CI: 1.10–1.25) and male (OR 8.58, 95% CI: 1.58–68.9).ConclusionThere was no association between COPD and definite ILA. However, low-dose CT signs of lung fibrosis were also observed in COPD, and their clinical relevance is yet to be determined.

CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

Many patients with chronic obstructive pulmonary disease (COPD) have marked discordance between forced expiratory volume in 1 second (FEV1) and degree of emphysema on computed tomography (CT). Biomechanical differences between these patients have not been studied. We aimed to identify reasons for the discordance between CT and spirometry in some patients with COPD. Subjects with Global initiative for chronic Obstructive Lung Disease stages I-IV from a large multicenter study (The Genetic Epidemiology of COPD) were arranged by percentiles of %predicted FEV1 and emphysema on CT. Three categories were created using differences in percentiles: Catspir with predominant airflow obstruction/minimal emphysema, CatCT with predominant emphysema/minimal airflow obstruction, and Catmatched with matched FEV1 and emphysema. Image registration was used to derive Jacobian determinants, a measure of lung elasticity, anisotropy, and strain tensors, to assess biomechanical differences between groups. Regression models were created with the previously mentioned categories as outcome variable, adjusting for demographics, scanner type, quantitative CT-derived emphysema, gas trapping, and airway thickness (model 1), and after adding biomechanical CT metrics (model 2). Jacobian determinants, anisotropy, and strain tensors were strongly associated with FEV1. With Catmatched as control, model 2 predicted Catspir and CatCT better than model 1 (Akaike information criterion 255.8 vs. 320.8). In addition to demographics, the strongest independent predictors of FEV1 were Jacobian mean (β = 1.60,95%confidence intervals [CI] = 1.16 to 1.98; P < 0.001), coefficient of variation (CV) of Jacobian (β = 1.45,95%CI = 0.86 to 2.03; P < 0.001), and CV of strain (β = 1.82,95%CI = 0.68 to 2.95; P = 0.001). CVs of Jacobian and strain are both potential markers of biomechanical lung heterogeneity. CT-derived measures of lung mechanics improve the link between quantitative CT and spirometry, offering the potential for new insights into the linkage between regional parenchymal destruction and global decrement in lung function in patients with COPD.

Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality; however, the role of inflammatory mediators in its pathobiology remains unclear. The aim of this study was to investigate the influence of gender in COPD on lipid mediator levels.Bronchoalveolar lavage fluid (BALF) and serum were obtained from healthy never-smokers, smokers and COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage I-II/A-B) (n=114). 94 lipid mediators derived from the cytochrome-P450, lipoxygenase, and cyclooxygenase pathways were analysed by liquid chromatography-mass spectrometry.Multivariate modelling identified a 9-lipid panel in BALF that classified female smokers with COPD from healthy female smokers (p=6×10(-6)). No differences were observed for the corresponding male population (p=1.0). These findings were replicated in an independent cohort with 92% accuracy (p=0.005). The strongest drivers were the cytochrome P450-derived epoxide products of linoleic acid (leukotoxins) and their corresponding soluble epoxide hydrolase (sEH)-derived products (leukotoxin-diols). These species correlated with lung function (r=0.87; p=0.0009) and mRNA levels of enzymes putatively involved in their biosynthesis (r=0.96; p=0.003). Leukotoxin levels correlated with goblet cell abundance (r=0.72; p=0.028).These findings suggest a mechanism by which goblet cell-associated cytochrome-P450 and sEH activity produce elevated leukotoxin-diol levels, which play a putative role in the clinical manifestations of COPD in a female-dominated disease sub-phenotype.