Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Wan, Emily S.; Fortis, Spyridon; Regan, Elizabeth A.; Hokanson, John E.; Han, MeiLan K.; Casaburi, Richard; Make, Barry J.; Crapo, James D.; DeMeo, Dawn L.; Silverman, Edwin K.

doi:10.1164/rccm.201804-0663oc

Cited by 178 publications

(206 citation statements)

References 38 publications

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“…The results are consistent with the previously reported analysis of the COPDGene study that showed PRISm is an unstable classification which is associated with increased mortality compared to GOLD 1 COPD [12,13]. At 12.4%-12.5%, the prevalence of PRISm was higher in the COPDGene cohort than in the Rotterdam study, which might reflect different sampling schemes (clinical study centres in the former, population-based sampling in the latter) [12,13]. In a recent study in a large Danish cohort, ÇOLAK et al [14] found that even when FEV 1 /FVC >0.8, the presence of chronic respiratory symptoms is associated with respiratory-related hospitalisation and death.…”

supporting

confidence: 93%

Looking at the COPD spectrum through “PRISm”

Adibi

Sadatsafavi

2020

Eur Respir J

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]. COPD is a major burden globally. According to the Global Burden of Disease study, COPD caused 3.2 million deaths in 2015, accounting for 5% of all deaths worldwide, making it the third leading cause of death in the world [1]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines spirometrically confirmed COPD based on a forced expiratory volume during the first second (FEV 1) to a forced vital capacity (FVC) ratio smaller than 0.7 [2]. The severity of airflow obstruction is further defined through GOLD severity grades based on the ratio of FEV 1 to its predicted value, with GOLD 1, 2, 3 and 4 defined around cutoff points of 80%, 50%, and 30% [2]. While diagnostic and disease management decisions (e.g. therapeutic choices) demand definitions that create distinct categories, the physiological processes underlying COPD act on a continuous scale [3]. For example, it is recognised that patients fall on a continuous spectrum on the three major aspects of COPD: rate of lung function decline [4], frequency of acute COPD exacerbations [5] and symptom burden [6], with little correlation between the three. Categorising such a continuous process inevitably results in COPD phenotypes that are numerous, loosely defined, and not always mutually exclusive [7, 8].

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supporting

confidence: 93%

Looking at the COPD spectrum through “PRISm”

Adibi

Sadatsafavi

2020

Eur Respir J

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“…In our study, subjects with PRISm were similar to typical COPD patients with higher exacerbation frequency, higher comorbidity count, more symptoms, and worse baseline QoL compared to participants that had no airflow obstruction at baseline. Other studies have reported an increase in BMI [27], morbidity [28], increased airway wall thickness [29] and mortality [30] [31] in patients with restrictive spirometry compared to those with no lung disease. Prior data published from COPDGene has also shown that 25% of PRISm individuals developed obstruction between Phase 1 and Phase 2 follow up (31), highlighting the heterogenous nature of this group as well as the potential benefit of routine spirometry in these groups to detect early COPD.…”

Section: Discussionmentioning

confidence: 93%

Factors influencing decline in quality of life in smokers without airflow obstruction: The COPDGene study

Parekh

Bhatia

Cherrington

et al. 2020

Respiratory Medicine

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Current and former smokers with normal spirometry and with Preserved Ratio Impaired Spirometry (PRISm) experience respiratory events similar to chronic obstructive pulmonary disease (COPD) exacerbations. Exacerbations significantly reduce quality of life (QoL) in COPD patients however the effect of respiratory exacerbations on QoL in these groups is unknown. We hypothesized that exacerbations and change in exacerbation status would predict QoL decline among normal spirometry and PRISm participants in COPDGene. Methods: COPDGene is a multicenter, longitudinal study in the U.S. designed to identify genetic determinants of COPD. We enrolled study subjects in Phase 1 of COPDGene and performed multivariable logistic regression models to determine independent predictors of decline in quality of life [>4 points on the St George's Respiratory Questionnaire (SGRQ)]. Separate analyses were performed for current and former smokers with normal spirometry and PRISm. Frequent exacerbator status was defined by > 2 moderate or >1 severe exacerbations in the year prior to the baseline and year 5 follow-up visits. Results: Independent predictors of QoL deterioration included current smoking, higher exacerbation frequency, and a change from infrequent to frequent exacerbation status (REF: infrequent to infrequent exacerbation status) in both groups [PRISm (OR ¼ 3.15,95%CI, 1.67-5.94), normal spirometry (OR ¼ 4.72,95%CI, 3.25-6.86)]. A change from frequent to infrequent exacerbation status did not lower the odds of QoL decline in either cohort. Conclusion: Continued smoking and the onset of frequent exacerbations were predictors of QoL decline in smokers with normal spirometry and PRISm. Further studies are needed to identify modifiable factors associated with decline in QoL in smokers.

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“…(34,35) Many of these excluded individuals have PRISm, and although they do not meet the diagnostic spirometric criteria for COPD they exhibit similar changes such as small airways disease, emphysema and gas trapping. (4,36,37) Little focus has been given to whether asthma contributes to PRISm, despite high rates of selfreported asthma in other PRISm cohorts (21% in COPDgene (2) ) and in this UKBB cohort reported asthma among PRISm was 18.4%. (4) There are many plausible ways asthma could contribute to both PRISm and airflow obstruction.…”

Section: Discussionmentioning

confidence: 87%

Epidemiology and Genetics of Preserved Ratio Impaired SpiroMetry (PRISm): An Analysis of UK Biobank

Higbee¹,

Granell²,

Smith

et al. 2020

Preprint

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Rationale Preserved ratio impaired spirometry (PRISm) is defined as Forced Expiratory Volume in one second <80% predicted with a FEV1/Forced Vital Capacity of >0.70. It may be a precursor of COPD and has been associated with increased respiratory symptoms and comorbidities. Current understanding of PRISm is based on small selective cohorts and genetic determinants remain unknown. Objectives Identify the prevalence, risk factors, co-morbidity, and genetics of PRISm in a large cohort to improve power and generalizability. Methods The UKBiobank, provides a large cohort of genotyped individuals. Regression analysis determined risk factors for and associated co-morbidities of PRISm. Genome wide association studies, conditional, and gene-based analyses were performed with a PheWAS and literature search conducted on the results. Measurements and Main Results PRISm has a similar prevalence to airflow obstruction (8% vs 7.8%) and is associated with increased cardiovascular co-morbidity, OR of 1.26 (95%CI 1.20-1.31) after adjusting for BMI, smoking status, age, diabetes, and sex. Genetic analysis discovered four associated single nucleotide polymorphisms and eight genes. Two SNPs have not been described with respiratory disease before. Other genetic loci identified are known to increase risk of asthma and COPD, and influence response to inhaled steroids. Conclusions PRISm affects 8% of adults of whom ~40% report cardiovascular comorbidity. Detailed analysis reveals that PRISm has shared genetic associations with asthma and COPD. These findings highlight the need for research into the potential therapeutic strategies and screening for individuals with PRISm, in particular whether this may reduce transition to COPD and reduce cardiovascular disease.

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Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Abstract: PRISm is highly prevalent, is associated with increased mortality, and represents a transitional state for significant subgroups of subjects. Additional studies to characterize longitudinal progression in PRISm are warranted.

Cited by 178 publications

References 38 publications

Looking at the COPD spectrum through “PRISm”

Looking at the COPD spectrum through “PRISm”

Factors influencing decline in quality of life in smokers without airflow obstruction: The COPDGene study

Epidemiology and Genetics of Preserved Ratio Impaired SpiroMetry (PRISm): An Analysis of UK Biobank

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