Impaired Spirometry Research Articles

Clinical Characteristics and Medical Utilization of Smokers with Preserved Ratio Impaired Spirometry.

To investigate the clinical characteristics and medical utilization of smokers with preserved ratio impaired spirometry (PRISm). We used data from the Korean National Health and Nutrition Examination Survey between 2007 and 2012, linked to the Health Insurance Review and Assessment Service. Clinical characteristics and medical utilization, including inpatient admission, emergency department visit, prescribed medication, and medical cost, were retrospectively compared among three groups: normal spirometry, PRISm, and chronic obstructive pulmonary disease (COPD). A total of 7115 smokers were included (4743 normal spirometry, 689 PRISm, and 1683 COPD subjects). The mean age was the highest in the COPD group, followed by the PRISm and normal groups, and the proportion of women was the highest in the PRISm group. The tobacco exposure, socioeconomic status (SES), and schooling level of the PRISm group were at levels between those of the normal and COPD groups. However, the PRISm group had the highest proportion of current smokers, highest body mass index (BMI), and lowest mean FEV1 and FVC % predicted. During the study period, the medical utilization of 92 smokers (13.4%) in the PRISm group and 436 smokers (25.9%) in the COPD group was related to respiratory diseases. Emergency department visit or hospitalization and overall medical cost of the PRISm group were comparable to those of the COPD group, except for outpatient clinic visit. Old age, women, low BMI, low SES, low schooling level, high amount of tobacco exposure, wheezing, and decreased FEV1 and FVC % predicted were factors associated with medical utilization in PRISm. Medical utilization was comparable between the PRISm and COPD groups. Smokers with PRISm who were older, women, or heavy smokers with low BMI, low SES and schooling level, wheezing, or low FEV1 and FVC might need close observation and early treatment.

Associations between environmental heavy metals exposure and preserved ratio impaired spirometry in the U.S. adults

We examined 9556 individuals aged 18 to 79 years who had information on spirometry testing and heavy metals and used multivariable logistic or linear regression to evaluate associations between serum levels of cadmium, lead, and mercury and PRISm and lung function in U.S. adults, which were conducted first in all participants, and then separately in never/former smokers and current smokers. The overall prevalence of PRISm was 7.02%. High levels of serum cadmium were significantly associated with PRISm in all individuals, no matter in never/former smokers (quartile 4 vs 1, the OR = 2.517, 95% CI = 1.376–4.604, p-trend = 0.0077) and current smokers (quartile 4 vs 1, the OR = 2.201, 95% CI = 1.265–3.830, p-trend = 0.0020). Serum lead and mercury were not significantly correlated with PRISm, regardless of smoking status. Serum cadmium was strongly correlated with lower FEV1/FVC, regardless of smoking status. Besides, serum cadmium was also significantly related to lower FVC % predicted in never/former smokers and lower FEV1% predicted in current smokers. Serum lead was strongly correlated with lower FVC % predicted and FEV1/FVC in all individuals and never/former smokers. And serum mercury was significantly associated with decrements in FVC % predicted in all individuals and current smokers. These findings demonstrate that serum cadmium is associated with a higher risk of PRISm and lower lung function, with the most significant effect on FEV1/FVC in particular. Our results also indicate that exposure to lead and mercury negatively affects lung function in never/former smokers and current smokers, respectively.

Peripheral airway dysfunction in prematurity-associated obstructive lung disease identified by oscillometry.

Mechanisms underlying lung dysfunction after preterm birth are poorly understood. Studying phenotypes of prematurity-associated lung disease may aid understanding of underlying mechanisms. Preterm-born children with and without lung dysfunction and term controls were assessed using oscillometry before and after exercise, and after postexercise bronchodilation. Preterm-born children, born at gestation of 34 weeks or less, were classified into those with prematurity-associated obstructive lung disease (POLD; FEV1 < LLN, FEV1 /FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (pPRISm; FEV1 < LLN, FEV1 /FVC ≥ LLN) and compared to preterm (FEV1 ≥ LLN) and term controls (%predicted FEV1 > 90%). All children underwent cardiopulmonary exercise, and oscillometry assessment at baseline, postexercise, and after postexercise bronchodilator administration. From 241 participants aged 7-12 years, complete data were available from 179: 15 children with POLD and 11 with pPRISm were compared with 93 preterm and 60 term controls. POLD group, when compared to both control groups, had impaired impedance, greater resistance, more negative (greater magnitude) reactance at low frequencies, and also had decreased compliance. pPRISm group demonstrated impaired reactance and compliance compared to term controls. No differences were noted between the preterm and term controls. Exercise had little impact on oscillometry values, but children with POLD had greatest improvements after postexercise bronchodilator administration, with decreased resistance and decreased magnitude of reactance, particularly at low frequencies. Preterm-born children with obstructive airway disease had the greatest oscillometry impairments and the largest improvements after postexercise bronchodilator compared to control groups. Oscillometry can potentially be used to identify preterm-born children with lung disease to institute treatment.

Early Evidence of Chronic Obstructive Pulmonary Disease Obscured by Race-Specific Prediction Equations.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES race-specific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD.

Exploring Current Concepts and Challenges in the Identification and Management of Early-Stage COPD.

The need to improve health outcomes, as well as disease prognosis, has led clinicians and researchers to propose new ways of identifying COPD in its earliest forms. This initiative is based on the hypothesis that an earlier intervention would have a greater prognostic impact. However, the operational definition of a patient in the initial stages of the disease is complex, and there is still no unanimously accepted definition. GOLD has recently proposed different concepts to identify COPD in its early stages, such as COPD in young people or COPD with mild functional impairment. In addition, GOLD proposes two other concepts, called pre-COPD (symptomatic non-obstructive patients) and PRISm (preserved ratio with impaired spirometry), which aim to identify the patient at risk of developing this chronic airflow obstruction. However, despite the attractiveness of these concepts, none have been taken up universally by the medical community. A universally accepted identification of how to define COPD in its early stages is necessary as a preliminary step in order to design clinical trials to find out the best way to treat these patients. This review deals with these concepts of COPD at the onset of the disease, highlighting their importance and the problems involved in identifying them as therapeutic targets in real clinical practice.

Longitudinal Changes and Association of Respiratory Symptoms with Preserved Ratio Impaired Spirometry (PRISm): The Nagahama Study.

Rationale: Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objectives: To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. Methods: The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results: In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions: This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.

Preserved Ratio Impaired Spirometry and COPD Accelerate Frailty Progression: Evidence From a Prospective Cohort Study

Chronic obstructive pulmonary disease (COPD) was found to associate with frailty. However, there is inadequate longitudinal evidence for associations of COPD with frailty progression. Furthermore, recent studies revealed a new phenotype of lung function impairment: preserved ratio impaired spirometry (PRISm). Associations of PRISm and its transitions with frailty progression are unclear. What are the associations of PRISm, transitions of PRISm, and COPD with frailty progression? To analyze the associations of PRISm and COPD with frailty progression, 5,901 subjects were included from the English Longitudinal Study of Ageing. Subjects were classified into three lung function patterns of normal spirometry, PRISm, and COPD. Frailty progression was assessed by repeated measurements of the frailty index (FI) during follow-up. Among these 5,901 subjects, 3,765 subjects were included to analyze the associations of PRISm transitions with frailty progression. PRISm transitions were assessed based on the changes of lung function patterns after a four-year interval. Linear mixed-effect models were used for statistical analyses. The median follow-up periods were 9.5 years for the analyses of PRISm and COPD with frailty progression and 5.8 years for PRISm transitions with frailty progression. When compared with normal spirometry, subjects with PRISm and COPD presented accelerated FI progression with additional annual increases of 0.301(95%CI: 0.211 to 0.392, P<0.001) and 0.172(95%CI: 0.102 to 0.242, P<0.001), respectively. Subjects who transitioned from normal spirometry to PRISm also presented accelerated FI progression when compared with stable normal spirometry (β=0.242, 95%CI: 0.008 to 0.476, P=0.042). However, no accelerated FI progression was found in PRISm subjects who transitioned to normal spirometry (β=0.119, 95%CI: -0.181 to 0.418, P=0.438). Our findings indicate that PRISm and COPD are associated with accelerated frailty progression. Further studies are needed to elucidate the causality of PRISm and COPD with frailty.

Characterizing the urinary proteome of prematurity-associated lung disease in school-aged children

IntroductionAlthough different phenotypes of lung disease after preterm birth have recently been described, the underlying mechanisms associated with each phenotype are poorly understood. We, therefore, compared the urinary proteome for different spirometry phenotypes in preterm-born children with preterm- and term-born controls.MethodsPreterm and term-born children aged 7–12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) cohort, underwent spirometry and urine collection. Urine was analysed by Nano-LC Mass-Spectrometry with Tandem-Mass Tag labelling. The preterm-born children were classified into phenotypes of prematurity-associated preserved ratio impaired spirometry (pPRISm, FEV1 < lower limit of normal (LLN), FEV1/FVC ≥ LLN), prematurity-associated obstructive lung disease (POLD, FEV1 < LLN, FEV1/FVC < LLN) and preterm controls (FEV1 ≥ LLN,). Biological relationships between significantly altered protein abundances were analysed using Ingenuity Pathways Analysis software, and receiver operator characteristic curves were calculated.ResultsUrine was analysed from 160 preterm-born children and 44 term controls. 27 and 21 were classified into the pPRISm and POLD groups, respectively. A total of 785 proteins were detected. Compared to preterm-born controls, sixteen significantly altered proteins in the pPRISm group were linked to six biological processes related to upregulation of inflammation and T-cell biology. In contrast, four significantly altered proteins in the POLD group were linked with neutrophil accumulation. Four proteins (DNASE1, PGLYRP1, B2M, SERPINA3) in combination had an area under the curve of 0.73 for pPRISm and three combined proteins (S100A8, MMP9 and CTSC) had AUC of 0.76 for POLD.ConclusionsIn this exploratory study, we demonstrate differential associations of the urinary proteome with pPRISm and POLD.Trial registrationEudraCT: 2015-003712-20

The relationship between preserved ratio impaired spirometry and mortality in the myocardial infarction survivors: a population-based cohort study

IntroductionPreserved ratio impaired spirometry (PRISm) is a subtype of pulmonary function abnormality which is characterized by a proportional reduction in non-obstructive expiratory lung volume. Currently, no studies have shown a relationship between PRISm and mortality in myocardial infarction (MI) survivors.MethodsWe used cohort data from U.S. adults who attended the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. According to the ratio of forced expiratory volume in the first second (FEV1) to forced vital capacity (FVC), we divided lung function into normal spirometry (FEV1/ FVC) ≥ 70%, FEV1 ≥ 80%), PRISm (FEV1/FVC ≥ 70%, FEV1 < 80%) and obstructive spirometry (FEV1/FVC < 70%). Cox regression was used to estimate the correlation between lung functions and mortality among MI patients. Kaplan-Meier survival curves compared the prognosis of MI with three different lung functions. We further verify the stability of the results by sensitivity analysis.Results411 subjects were included in our research. The mean follow-up time for the study was 105 months. Compared with normal spirometry, PRISm was significantly correlated with a greater relative risk for all-cause mortality (adjust HR 3.41, 95% confidence interval [95%CI]: 1.76–6.60, P < 0.001) and cardiovascular mortality (adjust HR 13.9, 95%CI: 2.60–74.6, P = 0.002). PRISm remains more correlated with all-cause mortality (adjust HR 2.73, 95%CI: 1.28–5.83, P = 0.009) relative to obstructive spirometry. The results are basically stable after sensitivity analysis. Kaplan-Meier survival curves showed that patients with PRISm tended to have the lowest survival during the follow-up period.ConclusionPRISm is an independent risk factor for all-cause and cardiovascular mortality in MI survivors. The presence of PRISm was associated with a significantly higher risk of all-cause mortality compared with obstructive spirometry.

Preserved Ratio Impaired Spirometry and Risks of Macrovascular, Microvascular Complications and Mortality Among Individuals With Type 2 Diabetes

The prospective associations of preserved ratio impaired spirometry (PRISm) with new-onset macrovascular and microvascular complications and mortality among individuals with type 2 diabetes (T2D) and whether PRISm enhances the prediction ability of an established office-based risk score remain to be elucidated. Can PRISm be used as a predictor of poor prognosis in individuals with T2D? We included 20,047 study participants with T2D and complete data on spirometry at recruitment from the UK Biobank cohort. Multivariable Cox proportional hazards models were used to assess the associations of baseline PRISm (FEV1 to FVC ratio,≥ 0.70; FEV1,< 80%predicted) with subsequent risks of incident stroke (any type), ischemic stroke, myocardial infarction, unstable angina, coronary heart disease, diabetic retinopathy, diabetic kidney disease, all-cause mortality, cardiovascular mortality, and respiratory mortality. For this cohort analysis, 4,521 patients (22.55%of participants with T2D) showed comorbid PRISm at baseline. Over a median follow-up of 11.52 to 11.87 years, patients with T2D with PRISm at baseline showed higher risks than those with normal spirometry findings of various T2D complications developing and mortality; the adjusted hazard ratios for PRISm were 1.413 (95%CI, 1.187-1.681) for stroke (any type), 1.382 (95%CI, 1.129-1.690) for ischemic stroke, 1.253 (95%CI, 1.045-1.503) for myocardial infarction, 1.206 (95%CI, 1.086-1.339) for coronary heart disease, 1.311 (95%CI, 1.141-1.506) for diabetic retinopathy, 1.384 (95%CI, 1.190-1.610) for diabetic kidney disease, 1.337 (95%CI, 1.213-1.474) for all-cause mortality, 1.597 (95%CI, 1.296-1.967) for cardiovascular mortality, and 1.559 (95%CI, 1.189-2.044) for respiratory mortality, respectively. The addition of PRISm significantly improved the reclassification ability, based on the net reclassification index, of an office-based risk score by 15.53%(95%CI, 10.14%-19.63%) to 33.60%(95%CI, 20.90%-45.79%). Individuals 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.

Clinical Manifestations of Subjects With the Non-Specific Pulmonary Function Test Pattern

IntroductionNon-specific pattern (NSP) is a subgroup of preserved ratio impaired spirometry (PRISm) that requires a normal total lung capacity measurement. NSP has been historically classified as being an obstructive lung disease pattern. There has been heightened interest and investigation into PRISm recently as it has been associated with an increased likelihood of developing chronic obstructive pulmonary disease (COPD). Given the inherent challenges of understanding the clinical significance of the NSP, the aim of this study was to further explore the clinical characteristics of patients with this pulmonary function test pattern. Material and methodsWe identified 111 and 79 subjects using pre-bronchodilator (pre-BD) and post-bronchodilator (post-BD) values, respectively, that met criteria for NSP. The outpatient medical records were retrospectively reviewed for associated diagnoses that were then clustered into ‘obstructive’ or ‘non-obstructive’ groups based on the treating physician's primary pulmonary clinical diagnosis. ResultsWithin this NSP cohort, cough, wheezing and sputum production were documented more frequently in those with an obstructive lung disease diagnosis. Whether identified using pre-BD or post-BD spirometric values, those with NSP and a positive BD response were more likely to carry an obstructive lung disease diagnosis. ConclusionApproximately one third of patients with NSP in this study were not given an obstructive lung disease diagnosis by their clinician, which supports the classification of NSP as not an exclusively obstructive lung disease pattern. However, the presence of supporting clinical symptoms, such as cough with sputum production and wheeze, and/or a positive BD response on PFT, support a diagnosis of obstruction in patients with NSP.

Trajectories of Spirometric Patterns, Obstructive and PRISm, in a Population-Based Cohort in Latin America.

Preserved ratio impaired spirometry (PRISm) has been associated with adverse outcomes and increased transition to other spirometric categories over time. We aimed to examine its prevalence, trajectories over time, and outcomes in a population-based sample from Latin America. Data were obtained from two population-based surveys of adults from three cities in Latin America (PLATINO study), conducted on the same individuals 5-9 years after their baseline examination. We estimated the frequency of PRISm defined by FEV1/FVC≥0.70 with FEV1 <80%, describing their clinical characteristics, longitudinal transition trajectories over time, factors associated with the transition. At baseline, 2942 participants completed post-bronchodilator spirometry, and 2026 at both evaluations. The prevalence of normal spirometry was 78%, GOLD-stage 1 10.6%, GOLD 2-4 6.5%, and PRISm was: 5.0% (95% CI 4.2-5.8). PRISm was associated with less schooling, more reports of physician-diagnosis of COPD, wheezing, dyspnea, missing days at work, having ≥2 exacerbations in the previous year but without accelerated lung function decline. Mortality risk was significantly higher in PRISm (HR 1.97, 95% CI 1.2-3.3) and COPD GOLD 1-4 categories (HR 1.79, 95% CI 1.3-2.4) compared with normal spirometry. PRISm at baseline most frequently transitioned to another category at follow-up (46.5%); 26.7% to normal spirometry and 19.8% to COPD. The best predictors of transition to COPD were closeness of FEV1/FVC to 0.70, older age, current smoking, and a longer FET in the second assessment. PRISm, is a heterogeneous and unstable condition prone to adverse outcomes that require adequate follow-up.

Causes of and Clinical Features Associated with Death in Tobacco Cigarette Users by Lung Function Impairment.

Rationale: Cigarette smoking contributes to the risk of death through different mechanisms. Objectives: To determine how causes of and clinical features associated with death vary in tobacco cigarette users by lung function impairment. Methods: We stratified current and former tobacco cigarette users enrolled in Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) into normal spirometry, PRISm (Preserved Ratio Impaired Spirometry), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-2 COPD, and GOLD 3-4 COPD. Deaths were identified via longitudinal follow-up and Social Security Death Index search. Causes of death were adjudicated after a review of death certificates, medical records, and next-of-kin interviews. We tested associations between baseline clinical variables and all-cause mortality using multivariable Cox proportional hazards models. Measurements and Main Results: Over a 10.1-year median follow-up, 2,200 deaths occurred among 10,132 participants (age 59.5 ± 9.0 yr; 46.6% women). Death from cardiovascular disease was most frequent in PRISm (31% of deaths). Lung cancer deaths were most frequent in GOLD 1-2 (18% of deaths vs. 9-11% in other groups). Respiratory deaths outpaced competing causes of death in GOLD 3-4, particularly when BODE index ⩾7. St. George's Respiratory Questionnaire score ⩾25 was associated with higher mortality in all groups: Hazard ratio (HR), 1.48 (1.20-1.84) normal spirometry; HR, 1.40 (1.05-1.87) PRISm; HR, 1.80 (1.49-2.17) GOLD 1-2; HR, 1.65 (1.26-2.17) GOLD 3-4. History of respiratory exacerbations was associated with higher mortality in GOLD 1-2 and GOLD 3-4, quantitative emphysema in GOLD 1-2, and airway wall thickness in PRISm and GOLD 3-4. Conclusions: Leading causes of death vary by lung function impairment in tobacco cigarette users. Worse respiratory-related quality of life is associated with all-cause mortality regardless of lung function.

Longitudinal mortality of preserved ratio impaired spirometry in a middle-aged Asian cohort

BackgroundAlthough preserved ratio impaired spirometry (PRISm) has been determined to have poor prognosis, it is a heterogeneous state, and studies regarding its prognosis in Asians are limited. This study investigated the long-term all-cause and cardiovascular mortality of patients with PRISm compared with those of patients with chronic obstructive pulmonary disease (COPD) and normal individuals in the Korean middle-aged general population.MethodsParticipants were recruited between 2001 and 2002 from a community-based prospective cohort in South Korea. Mortality data were collected over a 16.5-year mean follow-up period. The all-cause and cardiovascular mortality risks of PRISm were compared between patients with COPD and healthy controls.ResultsThe PRISm group had a mean age of 53.4 years and mean body mass index of 24.9 kg/m2; furthermore, 55.2% of the PRISm patients had never smoked, and the prevalence of comorbidities was not higher than that in the other groups. Compared with normal individuals, PRISm patients did not show increased all-cause mortality, whereas COPD patients showed increased all-cause mortality (PRISm: adjusted hazard ratio [aHR], 1.19; 95% confidence interval [CI], 0.85–1.65; COPD: aHR, 1.34, 95% CI, 1.07–1.69). Furthermore, the PRISm patients did not show increased cardiovascular mortality compared with normal individuals (PRISm: aHR, 1.65; 95% CI, 0.92–2.95; COPD: aHR, 1.83; 95% CI, 1.09–3.07).ConclusionIn our population-based cohort, all-cause and cardiovascular mortality risk did not increase in individuals with PRISm compared with normal individuals. Further studies are needed to distinguish a lower-risk subgroup of PRISm with certain characteristics, such as middle-aged, light-smoking Asians without additional cardiovascular risk.

Cardiac dysfunction mediators CXCL-9 and chemotaxis of phagocytes characterized patients with long-term pulmonary dysfunction after COVID-19.

Abstract Severe COVID-19 is characterized by marked cytokine release and pulmonary dysfunction; however, it is still unknown which mediators support post-COVID-19 pulmonary dysfunction. Our aim was to determine the signaling pathways associated with long-term pulmonary dysfunction in patients with COVID-19. Our cohort of 60 patients with COVID-19 were followed up at 4- and 12-months post infection. Pulmonary sequelae were analyzed by computed tomography (CT), diffusing capacity of carbon monoxide (DLCO), spirometry, 6-minute walk test (6MWT) and handgrip test. Cytokines, chemokines and blood tests parameters were also analyzed. Furthermore, signaling pathways associated with pulmonary dysfunction were identified by serum proteomics analysis using TimsTOF-Pro and ingenuity pathway analysis. Fourteen patients with CT and abnormal DLCO were classified as patients with long-term pulmonary dysfunction (LTPD), who also presented impaired spirometry tests, 6MWT and handgrip strength than patients without sequelae or patients with CT only. We observed that only CXCL-9 was significantly increased in LTPD patients in comparison with other groups. In addition, the main signaling pathways identified by proteomics in LTPD patients were associated with an immunothrombotic state related to cardiac dysfunction, migration of dysfunctional monocytes and reduced IFN-signaling. In summary, patients with LTPD presented a restrictive lung condition, with greater fatigue, lower aerobic capacity and muscle strength 4-months post-COVID-19. Our data suggest that patients with previous cardiac dysfunction who had severe o moderate COVID-19 are more susceptible to develop LTPD. PROYECTO COVID1005, ACT210085 y Fondecyt Regular 1211480.

Preserved Ratio Impaired Spirometry, Metabolomics, and the Risk of Type 2 Diabetes.

Whether baseline preserved ratio impaired spirometry (PRISm) is associated with the risk of developing type 2 diabetes (T2D) and if this association could be mediated by circulating metabolites remains to be elucidated. To measure the prospective association of PRISm with T2D and potential metabolic mediators thereof. This study used data from the UK Biobank and included 72 683 individuals without diabetes at baseline. PRISm was defined as the predicted forced expiratory volume in 1 second (FEV1) <80% and the FEV1/forced vital capacity ratio ≥0.70. Cox proportional hazards modeling was performed to assess the longitudinal relation between baseline PRISm and incident T2D. Mediation analysis was used to explore the mediation effects of circulating metabolites in the path from PRISm to T2D. During a median follow-up of 12.06 years, 2513 participants developed T2D. Individuals who had PRISm (N = 8394) were 47% (95% CI, 33%-63%) more likely to develop T2D compared with those who had normal spirometry (N = 64 289). A total of 121 metabolites showed statistically significant mediation effects in the path from PRISm to T2D (false discovery rate <0.05). Glycoprotein acetyls, cholesteryl esters in large high-density lipoprotein (HDL), degree of unsaturation, cholesterol in large HDL, and cholesteryl esters in very large HDL were the top 5 metabolic markers, with mediation proportions (95% CI) being 11.91% (8.76%-16.58%), 11.04% (7.34%-15.55%), 10.36% (7.34%-14.71%), 9.87% (6.78%-14.09%), and 9.51% (6.33%-14.05%), respectively. A total of 11 principal components that explained 95% variance of the metabolic signatures accounted for 25.47% (20.83%-32.19%) of the relation between PRISm and T2D. Our study revealed the association of PRISm with T2D risk and the potential roles of circulating metabolites in mediating this association.

Impaired Spirometry and COPD Increase the Risk of Cardiovascular Disease: A Canadian Cohort Study

Individuals with COPD and preserved ratio impaired spirometry (PRISm) findings in clinical settings have an increased risk of cardiovascular disease (CVD). Do individuals with mild to moderate or worse COPD and PRISm findings in community settings have a higher prevalence and incidence of CVD compared with individuals with normal spirometry findings? Can CVD risk scores be improved when impaired spirometry is added? The analysis was embedded in the Canadian Cohort Obstructive Lung Disease (CanCOLD). Prevalence of CVD (ischemic heart disease [IHD] and heart failure [HF]) and their incidence over 6.3 years were compared between groups with impaired and normal spirometry findings using logistic regression and Cox models, respectively, adjusting for covariables. Discrimination of the pooled cohort equations (PCE) and Framingham risk score (FRS) in predicting CVD were assessed with and without impaired spirometry. Participants (n= 1,561) included 726 people with normal spirometry findings and 835 people with impaired spirometry findings (COPD Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 disease, n= 408; GOLD stage≥ 2, n= 331; PRISm findings, n= 96). Rates of undiagnosed COPD were 84%in GOLD stage 1 and 58%in GOLD stage≥ 2 groups. Prevalence of CVD (IHD or HF) was significantly higher among individuals with impaired spirometry findings and COPD compared with those with normal spirometry findings, with ORs of 1.66 (95%CI, 1.13-2.43; P= .01∗) (∗ indicates statistical significane with P < .05) and 1.55 (95%CI, 1.04-2.31; P= .033∗), respectively. Prevalence of CVD was significantly higher in participants having PRISm findings and COPD GOLD stage≥ 2, but not GOLD stage 1. CVD incidence was significantly higher, with hazard ratios of 2.07 (95%CI, 1.10-3.91; P= .024∗) for the impaired spirometry group and 2.09 (95%CI, 1.10-3.98; P= .024∗) for the COPD group compared to individuals with normal spirometry findings. The difference was significantly higher among individuals with COPD GOLD stage≥ 2, but not GOLD stage 1. The discrimination for predicting CVD was low and limited when impaired spirometry findings were added to either risk score. Individuals with impaired spirometry findings, especially those with moderate or worse COPD and PRISm findings, have increased comorbid CVD compared with their peers with normal spirometry findings, and having COPD increases the risk of CVD developing.

How Important is Spirometry for Identifying Patients with COPD Appropriate for Palliative Care?

Providing palliative care to patients with chronic obstructive pulmonary disease (COPD) is a priority. Spirometry demonstrating airflow limitation is a diagnostic test for COPD and a common inclusion criterion for palliative care research. However, requiring spirometry with airflow limitation may exclude appropriate patients unable to complete spirometry, or patients with preserved-ratio impaired spirometry and symptoms or imaging consistent with COPD. To determine differences in quality of life (QOL) and symptoms between patients with COPD identified based on International Classification of Diseases (ICD) codes and spirometry with airflow limitation compared to ICD codes only. Patients with COPD enrolled in a palliative care trial were included. Patients were at high risk of hospitalization and death and reported poor QOL. Baseline measures of QOL (Functional Assessment of Cancer Therapy-General (FACT-G), the Clinical COPD Questionnaire, and Quality of Life at the End of Life), and symptoms (Patient Health Questionnaire-8, Generalized Anxiety Disorder-7, fatigue, Insomnia Severity Index) were compared. Two hundred eight patients with COPD were predominantly male, White, and average age was 68.4. Between patients with ICD codes and spirometry with airflow limitation compared to patients with ICD codes only, there were no significant differences in FACT-G (59.0 vs. 55.0, P=0.33), other measures of QOL, or symptoms between groups. These results imply that spirometry may not need to be a requirement for inclusion into palliative care research or clinical care for patients with poor quality of life and at high risk for adverse outcomes.

Preserved ratio impaired spirometry with or without restrictive spirometric abnormality

Preserved ratio impaired spirometry (PRISm) is defined by reduced FEV1 with a preserved FEV1/FVC ratio; some individuals with PRISm can also have restrictive ventilatory abnormality. The aim of this study was to clarify clinical features of restrictive and non-restrictive PRISm. In total, 11,246 participants (mean, 49.1 years; range, 35–65 years) from five healthcare centres were included in this study. We evaluated baseline characteristics of participants with restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1 < 80% and FVC < 80%) and non-restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1 < 80% and FVC ≥ 80%), and airflow obstruction (FEV1/FVC < 0.7). We examined the longitudinal risk of developing airflow obstruction by comparing spirometry results at baseline and 5 years post-baseline among 2141 participants. Multivariate analysis demonstrated that a history of asthma or smoking could constitute an independent risk factor for non-restrictive PRISm, and that non-restrictive PRISm was independently associated with the risk of developing airflow obstruction. In contrast, female sex, advanced age, and high BMI, but not history of asthma or smoking, were risk factors for restrictive PRISm. Restrictive PRISm was not associated with the development of airflow obstruction. In conclusion, our results indicate that PRISm can be categorized according to the presence or absence of restrictive abnormality. Non-restrictive PRISm, which does not meet the conventional criteria of obstructive and restrictive ventilatory abnormalities, may be a precursor of chronic obstructive pulmonary disease and merits increased monitoring.

Association between preserved ratio impaired spirometry and sleep apnea in a Chinese community

Objective This study investigated the association between obstructive sleep apnea (OSA) and preserved ratio impaired spirometry (PRISm) in a community population. Methods Baseline data from a prospective cohort study, the Predictive Value of Combining Inflammatory Biomarkers and Rapid Decline of FEV1 for COPD (PIFCOPD), were used for cross-sectional analysis. Participants aged 40–75 years were recruited from the community and their demographic information and medical history were collected. The STOP-Bang questionnaire (SBQ) was used to assess the risk of OSA. Pulmonary function tests were performed using a portable spirometer (COPD-6) and forced expiratory volume in 1 s (FEV1) and 6 s (FEV6) were measured. Routine blood, biochemical, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 tests were also performed. The pH of the exhaled breath condensate was determined. Results A total of 1183 participants were enrolled, of which 221 with PRISm and 962 with normal lung function. The neck circumference, waist-to-hip ratio, hs-CRP concentration, proportion of males, cigarette exposure, number of current smoker, high risk of OSA, and prevalence of nasal and ocular allergy symptoms were significantly higher in the PRISm group than in the non-PRISm group (p < .05). Logistic regression showed that the risk of OSA (odds ratio, 1.883; 95% confidence interval, 1.245–2.848), waist-to-hip ratio, current smoking, and prevalence of nasal allergy symptoms were independently associated with PRISm after correcting for age and sex. Conclusion These findings showed that OSA prevalence is independently associated with PRISm prevalence. Further studies should confirm the relationship between systemic inflammation in OSA, localized inflammation of the airways, and impaired lung function.