Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline

Hayden, Lystra P.; Hardin, Megan; Qiu, Weiliang; Lynch, David A.; Strand, Matthew; Beek, Edwin Jr van; Crapo, James D.; Silverman, Edwin K.; Hersh, Craig P.; Investigators, COPDGene

doi:10.1016/j.chest.2017.11.038

Cited by 16 publications

(14 citation statements)

References 25 publications

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“…There has been a growing interest in the risk of early life asthmatics for developing COPD, and thus ACO, in adulthood [ 15 ]. It has been proposed that in some childhood asthmatics, the risk for COPD is the result of the lungs never achieving their expected growth and development in early adulthood [ 11 , 12 , 16 , 20 , 52 , 53 ]. Normal decline in lung function can lead to COPD since expected maximal FEV 1 is never attained.…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were asked if they had ever had asthma, at what age it started, and if it was diagnosed by a doctor or other health professional. Childhood asthma was defined as self-report of asthma diagnosed by a health professional with age of onset at < 16 years or as a child with exact age not known [ 5 , 16 , 20 , 33 ]. Subjects were classified as never having asthma if they responded “No” to asthma history on the questionnaire.…”

Section: Methodsmentioning

confidence: 99%

“…Subjects were classified as never having asthma if they responded “No” to asthma history on the questionnaire. As in previous COPDGene publications, COPD was defined as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007 spirometry grades 2–4, corresponding to post-bronchodilator forced expiratory volume in the first second (FEV 1 ) to forced vital capacity (FVC) ratio < 0.7 with FEV 1 < 80% predicted [ 16 – 18 , 20 , 34 ]. Control smokers had normal spirometry, defined as FEV 1 /FVC ≥ 0.7 and FEV 1 ≥ 80%.…”

Section: Methodsmentioning

confidence: 99%

“…We demonstrated that that ACO subjects were younger with a lower lifetime smoking intensity, and that both childhood asthmatics and ACO subjects have increased airways disease on chest computed tomography scan [ 17 – 19 ]. Longitudinal analysis has shown that early-life asthmatics do not have increased rates of lung function decline despite their increased exacerbation frequency [ 20 ]. We have not previously examined childhood asthma as an independent risk factor for COPD in this population.…”

Section: Introductionmentioning

confidence: 99%

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Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

et al. 2018

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BackgroundChildhood asthma is strongly influenced by genetics and is a risk factor for reduced lung function and chronic obstructive pulmonary disease (COPD) in adults. This study investigates self-reported childhood asthma in adult smokers from the COPDGene Study. We hypothesize that childhood asthma is associated with decreased lung function, increased risk for COPD, and that a genome-wide association study (GWAS) will show association with established asthma variants.MethodsWe evaluated current and former smokers ages 45–80 of non-Hispanic white (NHW) or African American (AA) race. Childhood asthma was defined by self-report of asthma, diagnosed by a medical professional, with onset at < 16 years or during childhood. Subjects with a history of childhood asthma were compared to those who never had asthma based on lung function, development of COPD, and genetic variation. GWAS was performed in NHW and AA populations, and combined in meta-analysis. Two sets of established asthma SNPs from published literature were examined for association with childhood asthma.ResultsAmong 10,199 adult smokers, 730 (7%) reported childhood asthma and 7493 (73%) reported no history of asthma. Childhood asthmatics had reduced lung function and increased risk for COPD (OR 3.42, 95% CI 2.81–4.18). Genotype data was assessed for 8031 subjects. Among NHWs, 391(7%) had childhood asthma, and GWAS identified one genome-wide significant association in KIAA1958 (rs59289606, p = 4.82 × 10− 8). Among AAs, 339 (12%) had childhood asthma. No SNPs reached genome-wide significance in the AAs or in the meta-analysis combining NHW and AA subjects; however, potential regions of interest were identified. Established asthma SNPs were examined, seven from the NHGRI-EBI database and five with genome-wide significance in the largest pediatric asthma GWAS. Associations were found in the current childhood asthma GWAS with known asthma loci in IL1RL1, IL13, LINC01149, near GSDMB, and in the C11orf30-LRRC32 region (Bonferroni adjusted p < 0.05 for all comparisons).ConclusionsChildhood asthmatics are at increased risk for COPD. Defining asthma by self-report is valid in populations at risk for COPD, identifying subjects with clinical and genetic characteristics known to associate with childhood asthma. This has potential to improve clinical understanding of asthma-COPD overlap (ACO) and enhance future research into ACO-specific treatment regimens.Trial registrationClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0890-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

et al. 2018

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“…The prevalence of eosinophilic COPD is uncertain as different studies have used different criteria and eosinophil measurements, but in two COPD cohorts the prevalence was around 15% of patients . There is evidence that eosinophilic COPD patients and those with a history of prior asthma have more frequent exacerbations, but this has not been confirmed in other studies in which increased blood eosinophil counts were not related to the frequency of severe exacerbations . In the Copenhagen General Population Study there was an increase in exacerbations when blood eosinophils were >340/μL, and this was also seen in the large COPDGene and ECLIPSE cohorts …”

Section: Eosinophilic Copdmentioning

confidence: 90%

Inflammatory endotypes in COPD

Barnes

2019

Allergy

197

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Chronic obstructive pulmonary disease (COPD) is a major global health problem that is poorly treated by current therapies as it has proved difficult to treat the underlying inflammation, which is largely corticosteroid-resistant in most patients. Although rare genetic endotypes of COPD have been recognized, despite the clinical heterogeneity of COPD, it has proved difficult to identify distinct inflammatory endotypes.Most patients have increased neutrophils and macrophages in sputum, reflecting the increased secretion of neutrophil and monocyte chemotactic mediators in the lungs.However, some patients also have increased eosinophils in sputum and this may be reflected by increased blood eosinophils. Increased blood and sputum eosinophils are associated with more frequent exacerbations and predict a good response to corticosteroids in reducing and treating acute exacerbations. Eosinophilic COPD may represent an overlap with asthma but the mechanism of eosinophilia is uncertain as, although an increase in sputum IL-5 has been detected, anti-IL-5 therapies are not effective in preventing exacerbations. More research is needed to link inflammatory endotypes to clinical manifestations and outcomes in COPD and in particular to predict response to precision medicines. K E Y W O R D Sasthma-COPD overlap, eosinophil, exacerbations, interleukin-5, macrophage, neutrophil

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