scholarly journals Low miR-150-5p and miR-320b Expression Predicts Reduced Survival of COPD Patients

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1162 ◽  
Author(s):  
Andreas Keller ◽  
Nicole Ludwig ◽  
Tobias Fehlmann ◽  
Mustafa Kahraman ◽  
Christina Backes ◽  
...  
Keyword(s):  
Chronic Obstructive ◽  
Expression Change ◽  
Obstructive Pulmonary Disease ◽  
Risk Of Death ◽  
Copd Patients ◽  
Genome Wide ◽  
Increased Risk ◽  
Individual Survival ◽  
Molecular Profiles

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of death, reducing life expectancy on average between 5 and 7 years. The survival time after diagnosis, however, varies considerably as a result of the heterogeneity of COPD. Therefore, markers that predict individual survival of COPD patients are of great value. We analyzed baseline molecular profiles and collected 54 months of follow-up data of the cohort study “COPD and SYstemic consequences-COmorbidities NETwork” (COSYCONET). Genome-wide microRNA signatures from whole blood collected at time of the inclusion in the study were generated for 533 COPD patients including patients that deceased during the 54-month follow-up period (n = 53) and patients that survived this period (n = 480). We identified two blood-born microRNAs (miR-150-5p and miR-320b) that were highly predictive for survival of COPD patients. The expression change was then confirmed by RT-qPCR in 245 individuals. Ninety percent of patients with highest expression of miR-150-5p survived the 54-month period in contrast to only 50% of patients with lowest expression intensity. Moreover, the abundance of the oncogenic miR-150-5p in blood of COPD patients was predictive for the development of cancer. Thus, molecular profiles measured at the time of a COPD diagnosis have a high predictive power for the survival of patients.

Relation between Chronic Obstructive Pulmonary Disease and Peripheral Arterial Disease among Construction Workers

2021 ◽  
Vol 15 (10) ◽  
pp. 3473-3475
Author(s):  
U. Sivakumar ◽  
Rinku Garg ◽  
Sunita Nighute
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Peripheral Arterial Disease ◽  
Pulmonary Disease ◽  
Arterial Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
Peripheral Arterial

Introduction: PAD was asymptomatic in a large proportion of COPD patients and was associated with more severe lung disease than in COPD subjects without PAD. Materials and Methods: This was a Cross-sectional study conducted at Department of Physiology, Santosh Medical College diagnosed with COPD using Spirometry was recruited for the study with a Sample size of 130 patients. Results: The characteristics of the population for follow-up (n=130) are presented in table 1. The mean Mean±SD was 51.73±6.1 years. The prevalence of never smokers was 21.5%, former smokers were 51.5% and current smokers were 26.9%. In total, 41 out of 130 individuals (31.5%) had PAD based on an ABI of less than 0.6. A statistically significant association was found between COPD and newly diagnosed PAD during follow-up. The association between COPD and incident PAD was stronger (adjusted OR 1.91, 95% CI 1.14–3.21). Stratified analysis by smoking status revealed that the overall association between COPD and newly developed PAD was driven by the ever smoker group. Conclusion: Subjects with COPD have a higher risk of developing PAD. People with both COPD and PAD have a substantially increased risk of death. Consequently, early detection of PAD and preventive actions in people with COPD should receive more attention in clinical respiratory care. Keywords: Peripheral Arterial Disease, Chronic Obstructive Pulmonary Disease, Ankle-brachial index.

scholarly journals Risk and clinical predictors of osteoporotic fracture in East Asian patients with chronic obstructive pulmonary disease: a population-based cohort study

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2634 ◽  
Author(s):  
Ping-Hsueh Lee ◽  
Victor C. Kok ◽  
Po-Liang Chou ◽  
Ming-Chang Ku ◽  
Yu-Ching Chen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cohort Study ◽  
East Asian ◽  
Population Based ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Asian Patients ◽  
Copd Patients ◽  
Increased Risk

IntroductionOsteoporosis is becoming an impending epidemic in the Asia-Pacific region. The association between risk of osteoporotic fracture (OTPF) and chronic obstructive pulmonary disease (COPD) in East Asian patients is yet to be fully examined. We conducted a nationwide population-based retrospective cohort study of 98,700 patients aged ≥50 years with or without COPD using a national administrative claims dataset.Materials and MethodsThe patients were divided into COPD and comparison groups comprising 19,740 and 78,960 patients, respectively. The groups were 1 to 4 matched for age, gender, index date, diabetes mellitus, pre-existing osteoporosis and chronic kidney disease. Information such as the geographic area where southern part represented more sunshine exposure, smoking-related diagnoses, alcohol use disorder, whether there was regular use of inhaled corticosteroids and oral corticosteroids, vitamin D prescriptions, Charlson-Deyo comorbidity index score, and other relevant medical comorbidities were extracted for analysis. They were followed up until OTPF or the end of the year 2013. The outcome measure was an osteoporotic vertebral fracture and other long-bone fractures. A multivariate Cox model was constructed to derive adjusted hazard ratios (aHR) for OTPF with corresponding 95% confidence intervals (CI) after controlling for age, sex, insurance premium category, vitamin D prescription, osteoporosis, and coronary heart disease (CHD). Kaplan–Meier curves of the probability of OTPF-free survival for each cohort were compared using the log-rank test. Patients with OTPF during the first follow-up year were excluded from the overall risk calculation. Contributing factors to the increased risk of OTPF in COPD patients were examined in a sensitivity analysis.ResultsAfter a total follow-up of 68,743 patient-years for the COPD group and 278,051 patient-years for the matched comparison group, the HR for OTPF was 1.24 (95% CI [1.02–1.51];P = 0.0322) in COPD patients. The aHR was increased by 30% for vertebral OTPF (aHR = 1.297, 95% CI [1.020–1.649];P = 0.0339). Differential lag time sensitivity analysis revealed a progressively elevated risk up to 8-fold increase in women (aHR = 8.0 (95% CI [1.81–35.4];P < 0.01)) during the fifth follow-up year. COPD patients with pre-existing osteoporosis or given vitamin D prescription harbor a sustained increased risk up to the 5th (aHR, 4.1; 95% CI [1.61–10.35]) and third (aHR, 2.97; 95% CI [1.48–5.97]) follow-up year, respectively.ConclusionsOur nationwide population-based cohort study demonstrates that East Asian COPD patients aged 50 and beyond do harbor a modestly increased risk for osteoporotic vertebral fractures particularly for those who are female, have pre-existing osteoporosis or require vitamin D prescription.

scholarly journals Persistently elevated exhaled nitric oxide fraction is associated with increased risk of exacerbation in COPD

2018 ◽  
Vol 51 (1) ◽  
pp. 1701457 ◽  
Author(s):  
Bernardino Alcázar-Navarrete ◽  
Oliverio Ruiz Rodríguez ◽  
Pablo Conde Baena ◽  
Pedro José Romero Palacios ◽  
Alvar Agusti
Keyword(s):  
Nitric Oxide ◽  
Exhaled Nitric Oxide ◽  
Rank Test ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Increased Risk ◽  
Confounding Variables ◽  
Acute Exacerbations

Preventing the occurrence of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a major therapeutic goal. We hypothesise that persistently increased levels of exhaled nitric oxide (FeNO) during follow-up can identify a group of COPD patients at higher risk of AECOPD.To test this hypothesis, we measured FeNO levels (HypAir FeNO®, Medisoft; Sorinnes, Belgium) prospectively in 226 clinically stable COPD outpatients at recruitment and during follow-up (at 6 and 12 months). Patients were stratified according to the number of visits with FeNO ≥20 ppb.FeNO was <20 ppb in all three visits in 44.2% of patients, 29.6% in visit 1 and 26.1% in visit 2 or 3. These three groups suffered progressively higher AECOPD rates during follow-up (0.67, 0.91 and 1.42, respectively, p<0.001). After adjusting for potential confounding variables (log-rank test), the hazard ratio for AECOPD was higher in the latter group (1.579 (95% CI 1.049–2.378), p=0.029). Likewise, time to first moderate and severe AECOPD was shorter in these patients. Finally, there was no relationship between FeNO levels and circulating eosinophils.Persistent FeNO levels ≥20 ppb in clinically stable COPD outpatients are associated with a significantly higher risk of AECOPD.

scholarly journals Anemia, sarcopenia, physical activity, and the risk of tuberculosis in the older population: a nationwide cohort study

2021 ◽  
Vol 12 ◽  
pp. 204062232110159
Author(s):  
Jung Eun Yoo ◽  
Dahye Kim ◽  
Hayoung Choi ◽  
Young Ae Kang ◽  
Kyungdo Han ◽  
...  
Keyword(s):  
Physical Activity ◽  
Screening Program ◽  
Chronic Obstructive ◽  
Older Population ◽  
Timed Up And Go ◽  
Obstructive Pulmonary Disease ◽  
Mild Anemia ◽  
Increased Risk ◽  
Male Sex

Background: The aim of this study was to investigate whether physical activity, sarcopenia, and anemia are associated an with increased risk of tuberculosis (TB) among the older population. Methods: We included 1,245,640 66-year-old subjects who participated in the National Screening Program for Transitional Ages for Koreans from 2009 to 2014. At baseline, we assessed common health problems in the older population, including anemia and sarcopenia. The subjects’ performance in the timed up-and-go (TUG) test was used to predict sarcopenia. The incidence of TB was determined using claims data from the National Health Insurance Service database. Results: The median follow-up duration was 6.4 years. There was a significant association between the severity of anemia and TB incidence, with an adjusted hazard ratio (aHR) of 1.28 [95% confidence interval (CI), 1.20–1.36] for mild anemia and 1.69 (95% CI, 1.51–1.88) for moderate to severe anemia. Compared with those who had normal TUG times, participants with slow TUG times (⩾15 s) had a significantly increased risk of TB (aHR 1.19, 95% CI, 1.07–1.33). On the other hand, both irregular (aHR 0.88, 95% CI 0.83–0.93) and regular (aHR 0.84, 95% CI, 0.78–0.92) physical activity reduced the risk of TB. Male sex, lower income, alcohol consumption, smoking, diabetes, and asthma/chronic obstructive pulmonary disease increased the risk of TB. Conclusion: The risk of TB among older adults increased with worsening anemia, sarcopenia, and physical inactivity. Physicians should be aware of those modifiable predictors for TB among the older population.

scholarly journals LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoman Zhou ◽  
Yunjun Zhang ◽  
Yutian Zhang ◽  
Quanni Li ◽  
Mei Lin ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Polymorphisms ◽  
Chronic Obstructive ◽  
Nucleotide Polymorphisms ◽  
Obstructive Pulmonary Disease ◽  
Logistic Analysis ◽  
Copd Patients ◽  
Increased Risk ◽  
And Gender

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.

Abstract 16961: Time-dependent Markers of Chronic Obstructive Pulmonary Disease Severity and Change are Associated With Increased Risk of Mortality in the General Heart Failure Population: A National Study of 50,114 Patients From the United Kingdom

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Claire A Rushton ◽  
Lucy Riley ◽  
Duwarakan K Satchithananda ◽  
Peter W Jones ◽  
Umesh T Kadam
Keyword(s):  
Heart Failure ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Forced Expiration ◽  
Obstructive Pulmonary Disease ◽  
Gold Stage ◽  
Risk Of Mortality ◽  
Increased Risk

Purpose: Heart failure (HF) carries poor prognosis which changes over time. Chronic obstructive pulmonary disease (COPD) is common in HF and increases risk of mortality but how COPD severity and change influences HF prognosis is unknown. We hypothesised that in the HF general population, comorbidity stratification by increasing severity and longitudinal change would be associated with increased mortality. Methods: We used a case-control study nested within the UK Clinical Practice Research Datalink database (12-year time-period to 2014), of newly diagnosed HF patients aged over 40 years. Using risk set sampling, four controls were matched to cases on calendar and follow-up time. Routinely collected clinical measures of severity and change for COPD were (i) forced expiration volume in 1 second (FEV 1 ) stages, defined by Global Initiatives for Chronic Obstructive Lung Disease (GOLD) guidelines and (ii) prescribed medications in two time-windows covering 1-year prior to the match date. Conditional logistic regression was used to estimate risk ratios (RR) for all-cause mortality adjusted for known confounders. Results: Of the 50,114 HF sample, 5,848 (11.7%) had COPD and of these 62% died during follow-up compared to 52% of patients without COPD. COPD comorbidity risk associated with mortality stratified by GOLD stages was as follows: stage 1; adjusted RR 1.73 (95% CI 1.50-1.99) to stage 4; 3.14 (2.65, 3.73). Estimates for COPD FEV 1 change compared to no COPD were: GOLD stage same or better; 2.15 (1.97, 2.34) and GOLD stage worse; 2.70 (2.30, 3.17). The mortality estimates for medications severity were: inhalers only 1.13 (1.07,1.19), oral steroids; 1.83 (1.69,1.97) and oxygen; 2.94 (2.47, 3.51). The estimates for medications change were: no new steroids or oxygen; 1.22, (1.16, 1.28), new steroids but not oxygen; 1.84, (1.67,1.28) and new on oxygen; 3.41, (2.71,4.29). Conclusions: COPD is an important and common comorbidity in HF. Our results show that worse COPD severity and recent change based on routinely collected clinical data was associated with increased mortality and provides key prognostic information for clinical assessment in practice.

scholarly journals Heart Failure is Highly Prevalent and Difficult to Diagnose in Severe Exacerbations of COPD Presenting to the Emergency Department

2020 ◽  
Vol 9 (8) ◽  
pp. 2644
Author(s):  
Mariaenrica Tinè ◽  
Erica Bazzan ◽  
Umberto Semenzato ◽  
Davide Biondini ◽  
Elisabetta Cocconcelli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Emergency Department ◽  
Retrospective Chart Review ◽  
Care Program ◽  
Final Diagnosis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Factors Affecting ◽  
Risk Of Death ◽  
Copd Patients

Background: Some 20% of patients with stable Chronic Obstructive Pulmonary Disease (COPD) might have heart failure (HF). HF contribution to acute exacerbations of COPD (AECOPD) presenting to the emergency department (ED) is not well established. Aims: To assess (1) the HF incidence in patients presenting to the ED with AECOPD; (2) the concordance between ED and respiratory ward (RW) diagnosis; (3) the factors associated with risk of death after hospital discharge. Methods: Retrospective chart review of 119 COPD patients presenting to ED for acute exacerbation of respiratory symptoms and then admitted to RW where a final diagnosis of AECOPD, AECOPD and HF and AECOPD and OD (other diagnosis), was obtained. ED and RW diagnosis were then compared. Factors affecting survival at follow-up were investigated. Results: At RW, 40.3% of cases were diagnosed of AECOPD, 40.3% of AECOPD and HF and 19.4% of AECOPD and OD, with ED diagnosis coinciding with RW’s in 67%, 23%, and 57% of cases respectively. At RW, 60% of patients in GOLD1 had HF, of which 43% were diagnosed at ED, while 40% in GOLD4 had HF that was never diagnosed at ED. Lack of inclusion in a COPD care program, HF, and early readmission for AECOPD were associated with mortality. Conclusions: HF is highly prevalent and difficult to diagnose in patients in all GOLD stages presenting to the ED with severe AECOPD, and along with lack of inclusion in a COPD care program, confers a high risk for mortality.

Periodontitis Is Associated with Chronic Obstructive Pulmonary Disease

2019 ◽  
Vol 98 (5) ◽  
pp. 534-540 ◽  
Author(s):  
K. Takeuchi ◽  
K. Matsumoto ◽  
M. Furuta ◽  
S. Fukuyama ◽  
T. Takeshita ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Population Attributable Fraction ◽  
Community Dwelling ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Increased Risk ◽  
Severe Periodontitis ◽  
The Relationship

Although they are known to share pathophysiological processes, the relationship between periodontitis and chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present study was to test the hypothesis that periodontitis is associated with a greater risk of development of COPD, when smoking is taken into account. The analysis in a 5-y follow-up population-based cohort study was based on 900 community-dwelling Japanese adults (age: 68.8 ± 6.3 [mean ± SD], 46.0% male) without COPD aged 60 or older with at least 1 tooth. Participants were classified into 3 categories according to baseline periodontitis severity (no/mild, moderate, and severe). COPD was spirometrically determined by a fixed ratio of <0.7 for forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and by FEV1/FVC below the lower limit of normal. Poisson regression was used to calculate the relative risk (RR) of developing COPD according to the severity of periodontitis. The population attributable fraction (PAF) was also calculated. During follow-up, 22 (2.4%) subjects developed COPD. Compared with no/mild periodontitis subjects, a significantly increased risk of COPD occurred among severe periodontitis subjects (RR = 3.55; 95% confidence interval [CI], 1.18 to 10.67), but no significant differences were observed between the no/mild and moderate categories (RR = 1.48; 95% CI, 0.56 to 3.90). After adjustment for potential confounders, including smoking intensity, the relationship between severe periodontitis and risk of COPD remained significant (RR = 3.51; 95% CI, 1.15 to 10.74). Likewise, there was a positive association of periodontitis severity with risk of COPD ( P for trend = 0.043). The PAF for COPD due to periodontitis was 22.6%. These data highlight the potential importance of periodontitis as a risk factor for COPD.

scholarly journals Chronic obstructive pulmonary disease and rheumatic diseases: A systematic review on a neglected comorbidity

2019 ◽  
Vol 9 ◽  
pp. 2235042X1882020 ◽  
Author(s):  
Irini Gergianaki ◽  
Ioanna Tsiligianni
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Primary Sjögren Syndrome ◽  
Copd Patients ◽  
Increased Risk ◽  
Health Quality

Background: Although, both chronic obstructive pulmonary disease (COPD) and rheumatic diseases (RDs) are common, and each has significant impact on patients’ overall health/quality of life, their co-occurrence has received little attention, while 15% of COPD remains undiagnosed in RDs. Objective: To update the information regarding the comorbid state of RD/COPD (prevalence, incidence), to examine whether patients with RD have increased risk of developing COPD and vice versa, and what implications this comorbidity has on patients’ outcomes (mortality, hospitalizations, exacerbations). Methods: We performed a systematic literature review regarding the comorbidity of an RD (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), primary Sjogren syndrome disease (pSS), and systemic sclerosis (SSc)) with COPD. From 2803 reports retrieved, 33 articles were further screened. Finally, 27 articles were included. Results: Robust evidence supports that COPD develops up to 68% more frequently in patients with RA, as compared to the general population. Similarly, COPD is increased in every other RD that was studied. Further, self-referred arthritis is more common in COPD patients versus non-COPD controls and a predictor of worst self-rated health status. Patients with inflammatory arthritis/COPD have increased mortality (threefold in RA-COPD, irrespectively of which is first diagnosed), hospitalizations, and emergency visits. Conclusion: COPD is more common in patients with RA, AS, PsA, SLE, pSS, and SSc; yet, the association, vice versa, warrants further investigation. Nevertheless, COPD/RDs coexistence has significant prognostic value for worst outcomes; therefore, awareness is required to track early identification, especially in primary care.

scholarly journals Increased respiratory symptoms in COPD patients living in the vicinity of livestock farms

2015 ◽  
Vol 46 (6) ◽  
pp. 1605-1614 ◽  
Author(s):  
Floor Borlée ◽  
C. Joris Yzermans ◽  
Christel E. van Dijk ◽  
Dick Heederik ◽  
Lidwien A.M. Smit
Keyword(s):  
Respiratory Symptoms ◽  
Respiratory Health ◽  
Personal Characteristics ◽  
Chronic Obstructive ◽  
Livestock Farming ◽  
Obstructive Pulmonary Disease ◽  
Livestock Farm ◽  
Copd Patients ◽  
Increased Risk ◽  
Livestock Farms

Several studies have investigated the effect of livestock farm emissions on the respiratory health of local residents, but results are inconsistent. This study aims to explore associations between the presence of livestock farms and respiratory health in an area of high-density livestock farming in the Netherlands. We focused especially on associations between farm exposures and respiratory symptoms within subgroups of potentially susceptible patients with a pre-existing lung disease.In total, 14 875 adults (response rate 53.4%) completed a questionnaire concerning respiratory health, smoking habits and personal characteristics. Different indicators of livestock farm exposures relative to the home address were computed using a geographic information system.Prevalence of chronic obstructive pulmonary disease (COPD) and asthma was lower among residents living within 100 m of a farm (OR 0.47, 95% CI 0.24–0.91 and OR 0.65, 95% CI 0.45–0.93, respectively). However, >11 farms in 1000 m compared to fewer than four farms in 1000 m (fourth quartileversusfirst quartile) was associated with wheezing among COPD patients (OR 1.71, 95% CI 1.01–2.89). Using general practitioners' electronic medical records, we demonstrated that selection bias did not affect the observed associations.Our data suggest a protective effect of livestock farm emissions on the respiratory health of residents. Nonetheless, COPD patients living near livestock farms reported more respiratory symptoms, suggesting an increased risk of exacerbations.

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