Preserved Ratio With Impaired Spirometry

FOR RELATED ARTICLE, SEE PAGE 1268Preserved ratio with impaired spirometry (PRISm) describes a spirometric classification that is used to identify a respiratory syndrome that shares many features with COPD but does not meet criteria for obstruction by the Global Initiative for Obstructive Lung Disease criteria. PRISm is typically defined as spirometry with an FEV1 to FVC ratio above 0.7 and a FEV1 less than 80% predicted. Up to 24% of those who ever smoked can be classified as PRISm with estimates in the general population that range from 7% to 12%.1Schwartz A. Arnold N. Skinner B. et al.Preserved ratio impaired spirometry in a spirometry database.Respir Care. 2021; 66: 58-65Crossref PubMed Scopus (23) Google Scholar Although PRISm is a heterogenous group, it is often associated with metabolic syndrome and with an increased prevalence of several comorbid conditions, which include obesity, OSA, congestive heart failure, type 2 diabetes (T2D), and coronary artery disease. Studies in the Genetic Epidemiology of COPD Study (COPDGene) and other cohorts reveal that PRIsm can be dynamic over time with some patients experiencing worsening airflow obstruction and progression to COPD, whereas other patients remain in the PRISm category or revert to a normal spirometric pattern.2Wan E.S. Fortis S. Regan E.A. et al.Longitudinal phenotypes and mortality in preserved ratio impaired spirometry in the COPDGene study.Am J Respir Crit Care Med. 2018; 198: 1397-1405Crossref PubMed Scopus (111) Google Scholar,3Marott J.L. Ingebrigtsen T.S. Colak Y. Vestbo J. Lange P. Trajectory of preserved ratio impaired spirometry: natural history and long-term prognosis.Am J Respir Crit Care Med. 2021; 204: 910-920Crossref PubMed Scopus (35) Google Scholar Those patients who remain in the PRISm group or in whom incident PRISm develops experience more frequent respiratory exacerbations, major adverse cardiac events, hospitalization, and death compared with those patients with persistently normal spirometry or resolved PRISm.3Marott J.L. Ingebrigtsen T.S. Colak Y. Vestbo J. Lange P. Trajectory of preserved ratio impaired spirometry: natural history and long-term prognosis.Am J Respir Crit Care Med. 2021; 204: 910-920Crossref PubMed Scopus (35) Google Scholar Although a few investigations note associations between individual spirometry parameters and outcomes in T2D,4Godfrey M.S. Jankowich M.D. The vital capacity is vital: epidemiology and clinical significance of the restrictive spirometry pattern.Chest. 2016; 149: 238-251Abstract Full Text Full Text PDF PubMed Google Scholar no studies to date have focused on baseline PRISm specifically as a risk factor for adverse vascular outcomes in a diabetic population. FOR RELATED ARTICLE, SEE PAGE 1268 In this issue of CHEST, Li et al5Li G. Janowich M.D. Wu L. et al.Preserved ratio impaired spirometry and risks of macrovascular, microvascular complications and mortality among individuals with type 2 diabetes.Chest. 2023; 164: 1268-1280Abstract Full Text Full Text PDF Scopus (1) Google Scholar use data from more than 20,000 participants with T2D in the United Kingdom Biobank to evaluate associations between PRISm at baseline and prospective vascular complications that occurred over a follow-up period of nearly 12 years. The authors report a PRISm prevalence of 22% in this cohort of participants with T2D, which is consistent with other publications that have examined PRISm in those who currently and formerly smoked but twice as high as what is reported in the general population.1Schwartz A. Arnold N. Skinner B. et al.Preserved ratio impaired spirometry in a spirometry database.Respir Care. 2021; 66: 58-65Crossref PubMed Scopus (23) Google Scholar There are a higher proportion of female patients and non-White participants in the PRISm group, which is also consistent with investigations in other cohorts.3Marott J.L. Ingebrigtsen T.S. Colak Y. Vestbo J. Lange P. Trajectory of preserved ratio impaired spirometry: natural history and long-term prognosis.Am J Respir Crit Care Med. 2021; 204: 910-920Crossref PubMed Scopus (35) Google Scholar,6Wan E.S. Hokanson J.E. Murphy J.R. et al.Clinical and radiographic predictors of GOLD-unclassified smokers in the COPDGene study.Am J Respir Crit Care Med. 2011; 184: 57-63Crossref PubMed Scopus (119) Google Scholar Among the PRISm group, 45% were those who ever smoked; 64% were obese. Regarding T2D history, PRISm participants report a longer duration of illness and increased use of hypoglycemic medications with worse disease control (higher hemoglobin A1c values). A larger percentage of the PRISm group report use of lipid-lowering medications. The authors found associations between baseline PRISm and incident development of several macrovascular disorders, which included strokes, myocardial infarctions, unstable angina, and congestive heart failure. Associations also exist between PRISm and microvascular disorders such as diabetic kidney disease and diabetic retinopathy. Mortality rate analyses show an increased risk of death in the PRISm group related to both cardiac and respiratory causes. The authors also examine the addition of PRISm to an office-based risk score that is used to predict the probability of future diabetic complications; PRISm increases the discriminatory value of the metric to identify at-risk patients. The strengths of this study include a large, well-characterized population; a protocolized spirometry method; long duration of follow-up period; examination of cause of death in the mortality rate analyses; and the robustness of the findings across multiple subgroups of interest that includes smoking status, duration of diabetes, sex, and age older or younger than 65 years. Weaknesses of the study include relatively limited ethnic diversity in the cohort, lack of data on the use of respiratory medications or supplemental oxygen, and lack of data on biomarkers of inflammation. The study from Li et al5Li G. Janowich M.D. Wu L. et al.Preserved ratio impaired spirometry and risks of macrovascular, microvascular complications and mortality among individuals with type 2 diabetes.Chest. 2023; 164: 1268-1280Abstract Full Text Full Text PDF Scopus (1) Google Scholar not only emphasizes the adverse outcomes associated with PRISm as a syndrome but also suggests that it may play a role in contributing to systemic vascular injury above and beyond what would be attributable to T2D alone. The underlying reasons for this finding are unclear but could be attributable to several possible mechanisms. Prior work that examined PRISm reports increased respiratory symptoms and reduced exertional capacity compared with those who smoke with normal spirometry.7Woodruff P.G. Barr R.G. Bleecker E. et al.Clinical significance of symptoms in smokers with preserved pulmonary function.N Engl J Med. 2016; 374: 1811-1821Crossref PubMed Scopus (473) Google Scholar Increased sedentarism is associated with worsened glycemic control and increased risk of macrovascular complications.8Katzmarzyk P.T. Church T.S. Craig C.L. Bouchard C. Sitting time and mortality from all causes, cardiovascular disease, and cancer.Med Sci Sports Exerc. 2009; 41: 998-1005Crossref PubMed Scopus (1196) Google Scholar,9van Dijk J.W. van Loon L.J. Exercise strategies to optimize glycemic control in type 2 diabetes: a continuing glucose monitoring perspective.Diabetes Spectr. 2015; 28: 24-31Crossref PubMed Scopus (29) Google Scholar Taken together, it is possible that PRISm patients are overall less active because of respiratory symptoms, which may explain worsened glycemic control and increased risk of vascular complications observed by Li et al. In the COPDGene cohort, the group of participants with PRISm appear similar in terms of age, demographics, and comorbidities to the population presented in the UK Biobank; however, the COPDGene dataset reveals that PRISm is associated with a lower resting oxygen saturation compared with participants classified as Global Initiative for Obstructive Lung Diease 0.6Wan E.S. Hokanson J.E. Murphy J.R. et al.Clinical and radiographic predictors of GOLD-unclassified smokers in the COPDGene study.Am J Respir Crit Care Med. 2011; 184: 57-63Crossref PubMed Scopus (119) Google Scholar Given this information, unidentified tissue hypoxia in the UK cohort may result in a release of inflammatory mediators and local vascular injury via recruitment of neutrophils and other immune cells.10Taylor C.T. Colgan S.P. Regulation of immunity and inflammation by hypoxia in immunological niches.Nat Rev Immunol. 2017; 17: 774-785Crossref PubMed Scopus (379) Google Scholar The resultant vascular injury would then increase risk of macrovascular and microvascular complications. Vascular injury also occurs by glycosylation of the vascular endothelium, which is implicated in development of both atherosclerotic diseases and pulmonary hypertension.11Aronson D. Rayfield E.J. How hyperglycemia promotes atherosclerosis: molecular mechanisms.Cardiovasc Diabetol. 2002; 1: 1Crossref PubMed Scopus (375) Google Scholar,12Meloche J. Courchesne A. Barrier M. et al.Critical role for the advanced glycation end-products receptor in pulmonary arterial hypertension etiology.J Am Heart Assoc. 2013; 2e005157Crossref PubMed Scopus (82) Google Scholar A study in COPDGene that examined pulmonary vascular disease in PRISm, by use of an imaging biomarker, found that participants with this biomarker have increased respiratory symptoms, more supplemental oxygen use, worsened exertional capacity, and increased risk of respiratory exacerbations and death.13Wade R.C. Simmons J.P. Boueiz A. et al.Pulmonary artery enlargement is associated with exacerbations and mortality in ever-smokers with preserved ratio impaired spirometry.Am J Respir Crit Care Med. 2021; 204: 481-485Crossref PubMed Scopus (3) Google Scholar Unidentified pulmonary hypertension would increase risk of vascular complications in the UK PRISm cohort through the previously described mechanisms of sedentarism and tissue hypoxia. T2D in conjunction with hyperlipidemia, obesity, hypertension, and coronary artery disease collectively are termed the “metabolic syndrome” and work synergistically to exacerbate tissue injury and promote vascular complications. PRISm has been associated with metabolic syndrome in multiple investigations but classically is not thought of as a component of the “metabolic syndrome.” The data presented by Li et al5Li G. Janowich M.D. Wu L. et al.Preserved ratio impaired spirometry and risks of macrovascular, microvascular complications and mortality among individuals with type 2 diabetes.Chest. 2023; 164: 1268-1280Abstract Full Text Full Text PDF Scopus (1) Google Scholar provide another example of the interlink between respiratory function parameters and cardiovascular risk. None declared. Preserved Ratio Impaired Spirometry and Risks of Macrovascular, Microvascular Complications and Mortality Among Individuals With Type 2 DiabetesCHESTVol. 164Issue 5PreviewIndividuals with T2D with comorbid PRISm, accounting for a considerable proportion of the population with T2D, showed significantly increased risks of adverse macrovascular and microvascular complications and mortality. Full-Text PDF