Ravi Kalhan

Northwestern University | NU · Division of Pulmonary and Critical Care

Introduction The current framework for investigating respiratory diseases is based on defining lung health as the absence of lung disease. In order to develop a comprehensive approach to prevent the development of lung disease, there is a need to evaluate the full spectrum of lung health spanning from ideal to impaired lung health. The American Lun...

Background Protective factors against the risk of bronchiectasis are unknown. A high level of cardiorespiratory fitness is associated with a lower risk of chronic obstructive pulmonary disease. But whether fitness relates to bronchiectasis remains, to the knowledge of the authors, unknown. Purpose To examine the association between cardiorespirator...

Background The associations of chronic cigarette smoking with blood pressure (BP) remain mixed. It is unclear whether a lack of examination of racial differences contributed to the mixed findings in previous studies. Black smokers metabolize nicotine at a slower rate than White smokers and racial discrimination contributes to nicotine dependence an...

Primary prevention and interception of chronic lung disease are essential in the effort to reduce the morbidity and mortality caused by respiratory conditions. In this review, we apply a life course approach which examines exposures across the life span to identify risk factors which are associated with not only chronic lung disease but also an int...

Background: Comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased medical costs and risk of exacerbations. This study compared COPD-related medical costs and exacerbations in high-cost, high-comorbidity patients with COPD receiving initial maintenance treatment (IMT) with umeclidinium/vilanterol...

Background Airflow obstruction is associated with cognitive dysfunction, but studies have not assessed how emphysema, a structural phenotype of lung disease, might be associated with cognitive function independent from pulmonary function measured by spirometry. We aimed to determine the relationship between the presence of visually detectable emphy...

Immunologic risk factors contribute to endothelial dysfunction and development of pulmonary vascular disease. Immune checkpoint inhibitors, used as immunotherapies for malignancies, have a wide range of reported immune-related adverse events. We retrospectively describe the impact of immune checkpoint inhibitors on the development of pulmonary vasc...

The association between lung disease and cardiovascular disease later in life has been well described. Both obstructive and restrictive lung physiology as measured with spirometry have been associated with cardiovascular disease and poor health outcomes.

Activation of toll-like receptors (TLR1, TLR5, TLR6) and downstream markers (CCR1, MAPK14, ICAM1) leads to increased systemic inflammation. Our objective was to study the association between the gene expression levels of these six genes and lung function (Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC) and FEV1/FVC). We s...

Background Smokers with chronic obstructive pulmonary disease (COPD) have smaller left ventricles (LVs) due to reduced preload. Skeletal muscle wasting is also common in COPD, but less is known about its contribution to LV size. Purpose To explore the relationships between CT metrics of emphysema, venous vascular volume, and sarcopenia with the LV...

The relationship between body weight and lung function is complex. Using a dyadic multilevel linear modeling approach, treating body mass index (BMI) and lung function as paired, within-person outcomes, we test the hypothesis that individuals with more rapid increase in BMI exhibit more rapid decline in lung function: forced expiratory volume in on...

Importance Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain. Objective To assess whe...

Background: The InforMing the Pathway of COPD Treatment (IMPACT) trial demonstrated lower moderate/severe exacerbation rates with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Since IMPACT was a global study, post-hoc an...

Background: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials. Methods: In this prospective, randomized trial, we assigned patients between the ages of 40...

Background: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-i...

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema...

Background: Peak lung function and rate of decline predict future airflow obstruction and non-respiratory comorbid conditions. Associations between lung function trajectories and emphysema have not been explored. Methods: Using data from the population-based CARDIA Study, we sought to describe the prevalence of visually ascertained emphysema at...

Importance According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial. Objective To determine the...

Background: Tobacco smoke exposure is associated with emphysema and pulmonary fibrosis, both of which are irreversible. We have developed a new objective CT analysis tool that combines densitometry with machine learning to detect high attenuation changes in visually normal appearing lung (NormHA) that may precede these diseases. Methods: We trai...

The COPD Foundation has tried to address gaps in chronic obstructive pulmonary disease (COPD) care by providing COPD Pocket Consultant Guide cards to U.S. health care providers. Since launching the card in 2007, there have been numerous updates and more than 800,000 of these cards have been distributed at no charge to health care professionals. The...

Telephone quitlines are an effective population-based strategy for smoking cessation, particularly among individuals with tobacco-related diseases such as chronic obstructive pulmonary disease (COPD). Expanding quitline services to provide COPD-focused self-management interventions is potentially beneficial; however, data are needed to identify spe...

Objective Continuing to smoke after a cancer diagnosis undermines prognosis. Yet few trials have tested Food and Drug Administration (FDA)‐approved tobacco use medications in this population. Extended use varenicline may represent an effective treatment for cancer patients who smoke given barriers to cessation including a prolonged time line for re...

Background Diminished peak lung function in young adulthood is a risk factor for future chronic obstructive pulmonary disease. The association between lung disease and cardiovascular disease later in life is well documented. Whether peak lung function measured in young adulthood is associated with risk of future cardiovascular events is unknown. M...

Table S1. Association Between Lung Function Measured at Examination Year 10 (Mean Age 35 y, Range 28–40 y) and the Development of Incident Cardiovascular Risk Factors by the Year 20 Examination Figure S1. Number of participants included in the analytic cohorts based on available data. CAC indicates coronary artery calcium; CC, common carotid IMT;...

Rationale: Chronic lower respiratory diseases (CLRD), including COPD and asthma, are the fourth leading cause-of-death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in COPD patients. Objectives: To test if albuminuria was associated with lung function decline and incident CLRD. Methods: Six US populat...

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), Afri...

Introduction The degree to which smokers quit successfully with varenicline is strongly associated with their adherence to the medication regimen. Thus, measuring varenicline adherence to identify smokers needing additional intervention is a priority. Few studies, however, have examined the validity of self-reported varenicline adherence, using a b...

Chronic lower respiratory diseases (CLRD) are the fourth leading cause-of-death in the US. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed pre-bronchodil...

Introduction: The degree to which smokers adhere to pharmacotherapy predicts treatment success. The development of interventions to increase adherence requires identification of predictors of treatment adherence, particularly among specific clinical populations. Methods: Using data from a 12-week open-label phase of a clinical trial of varenicli...

Background and aims: Long-term blood pressure variability (BPV) is associated with cardiovascular events independent of mean blood pressure (BP); however, little is known about its predictors. Methods: Using data from the CARDIA study, we investigated the association between peak lung-function and long-term BPV in 2917 individuals (mean age 24.8...

Introduction: Chronic obstructive pulmonary disease (COPD) is a tobacco-related disease associated with several comorbid conditions, including elevated rates of depression and anxiety. Psychological factors that commonly underlie nicotine dependence, depression, and anxiety may represent novel treatment targets, but have not yet been examined amon...

Respiratory research has historically focused on identifying risk factors for and treatment of established lung disease. Public health approaches to common conditions, however, mandate that health promotion is a central feature of disease prevention. While smoking initiation prevention and cessation efforts are essential to respiratory health promo...

Rationale: Large airway dimensions on computed tomography (CT) have been associated with lung function, symptoms, and exacerbations in COPD, and symptoms in smokers with preserved spirometry. Their prognostic significance in persons without lung disease remains undefined. Objectives: To examine associations between large airway dimensions on CT...

Introduction A substantial proportion of cancer patients continue to smoke after their diagnosis but few studies have evaluated correlates of nicotine dependence and smoking rate in this population, which could help guide smoking cessation interventions. Aim This study evaluated correlates of smoking rate and nicotine dependence among 207 cancer p...

Rationale: There are limited data on factors in young adulthood that predict future lung disease. Objective: To determine the relationship between respiratory symptoms, loss of lung health, and incident respiratory disease in a population-based study of young adults. Methods: Prospective data from 2749 participants in the Coronary Artery Risk...

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N=60,552), Africa...

Rationale Adiposity is associated with low lung function, but the longitudinal relationship between lung function and adiposity is inadequately studied. Objective To examine the bidirectional longitudinal associations between rapid decline in lung function and adiposity phenotypes in healthy adults. Methods This secondary analysis used a 25-year...

The COPD Foundation Pocket Consultant Guide (PCG) was first released in 2007 as a practice tool for use at point of service for clinicians, especially primary care clinicians diagnosing and treating patients with chronic obstructive pulmonary disease (COPD). Over the years, the PCG has been supplemented with a mobile app that presents the tool in a...

Introduction Chronic lung disease, often characterised by rapid decline in lung function, is associated with vascular endothelial dysfunction (characterised by moderate to severe excess urinary albumin excretion (eUAE) but their longitudinal relationship is inadequately studied. In a bidirectional longitudinal examination of healthy adults, we anal...

Objective: Smoking cessation treatment should be an important aspect of cancer care. In this study, we evaluated whether cancer-related disease factors adversely influence smoking cessation treatment. Methods: Smokers with cancer (within 5 years of diagnosis, any tumor site) were recruited for an ongoing trial of varenicline for smoking cessatio...

Rationale: Accurate reference values for spirometry are important, as the results are used for diagnosing common chronic lung diseases such as asthma and chronic obstructive pulmonary disease, estimating physiological impairment, and predicting all-cause mortality. Reference equations have been established for Mexican Americans but not for other H...

Novel pharmacotherapies introduce additional options to providers and patients in how to best treat chronic obstructive pulmonary disease (COPD). Emerging data question the role of inhaled corticosteroids in COPD treatment, particularly as combination dual bronchodilator pharmacotherapies demonstrate robust results. For those maximized on pharmacot...

Background: PAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma. Objective: We sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, an...

Background The ratio of the diameter of the pulmonary artery (PA) to the diameter of the aorta (PA:A) on computed tomography (CT) imaging is associated with both COPD exacerbation and pulmonary hypertension. The mechanisms of PA enlargement in COPD are poorly understood. Methods In this retrospective, single center study we evaluated pulmonary fun...

Background Evaluation of impaired left ventricular (LV) filling has focused on intrinsic causes of LV dysfunction; however, pulmonary vascular changes may contribute to reduced LV filling and dyspnea. We hypothesized that lower total pulmonary vascular volume (TPVV) on computed tomography (CT) would be associated with dyspnea and decrements in LV e...

Multivariate mean differences in LV end-diastolic volume per standard deviation lower total pulmonary vascular volume stratified by cumulative pack-years of smoking. Results are adjusted for age, sex, race/ethnicity, height, weight, education, CT scanner manufacturer, milliamperes, total cholesterol, high-density lipoprotein cholesterol, triglyceri...

Mean differences in left atrial volume, peak early diastolic strain rate, strain relaxation index, T1 time and extracellular volume fraction associated with a 1 standard deviation lower total pulmonary vascular volume on computed tomography, stratified by smoking status. Model 1: Adjusted for age, sex, race/ethnicity, height, weight, education, CT...

Characteristics of participants with LV parameters and pulmonary microvascular blood volume measured on MRI. Data are presented as % or mean±SD, except as noted. Abbreviations: HDL, high-density lipoprotein; COPD, chronic obstructive pulmonary disease; GOLD, Global initiative for chronic obstructive lung disease; IQR, interquartile range. *Calculat...

Study population. (TIF)

Generalized additive multivariate model of relationship between total pulmonary vascular volume and LV end-diastolic volume among ever-smokers (A) without emphysema and (B) with emphysema. Results are adjusted for age, sex, race/ethnicity, height, weight, education, CT scanner manufacturer, milliamperes, current smoking, pack-years, total cholester...

Sensitivity analysis for mean difference in LV end-diastolic volume (mL) per 1 standard deviation lower total pulmonary vascular volume for ever-smokers. Abbreviations: LV EF = left ventricular ejection fraction, FEV1 = forced expiratory capacity in 1 second, FVC = forced vital capacity, ACE = angiotensin converting enzyme, ARB = angiotensin II rec...

Selected characteristics of included participants by quintile of percent total pulmonary vascular volume. Data are presented as % or mean±SD, except as noted. Abbreviations: IQR, interquartile range; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; TPVV, total pulmonary vascular volume. *For ever-smokers reporting pack-years,...

Selected characteristics of MESA Exam 5 participants included and not included in this analysis. Data are presented as no. (%) or mean±SD, except as noted. Abbreviations: IQR, interquartile range; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; TPVV, total pulmonary vascular volume; LV, left ventricular. *Among ever-smokers...

Mean differences in LV parameters associated with a 1 standard deviation lower percent total pulmonary vascular volume, stratified by smoking status. Model 1: Adjusted for age, sex, race/ethnicity, height, weight, education, CT scanner manufacturer and milliamperes. Model 2: Additionally adjusted for total cholesterol, high-density lipoprotein chol...

Mean differences in LV parameters, left atrial volume and pulmonary vein area associated with a 1 SD lower pulmonary microvascular blood volume on MRI in an independent sample of ever-smokers (N = 142). Abbreviations: LV, left ventricular; EDV, end-diastolic volume. Model 1: Adjusted for age, sex, race/ethnicity, height, weight, education and cohor...

Rationale: Beyond the risks of smoking, there are limited data on factors associated with change in lung function over time. Objective: To determine whether cardiorespiratory fitness was longitudinally associated with preservation of lung health. Methods: Prospective data from 3332 participants in the Coronary Artery Risk Development in Young...

Rationale: Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death in the United States. Emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined COPD but no available medications target emphysema. Transforming growth factor beta (TGF-β)...

The prognostic significance of acute pulmonary events in people with lower extremity peripheral artery disease (PAD) is unknown. We hypothesized that an acute pulmonary event (hospitalization for pneumonia and/or chronic lower respiratory disease (CLRD) exacerbation) would be associated with a higher rate of subsequent ischemic heart disease (IHD)...

Background: Airway wall thickening and lumen narrowing have been associated with COPD and asthma, but the prognostic significance of large airway structure is unclear. Aim: To test if airway measures on CT were associated longitudinally with physiologic, anatomic, and clinical outcomes in the general population. Methods: MESA recruited participants...

Introduction: COPD is a major cause of morbidity and mortality, yet risk factors in the general population beyond smoking are poorly defined. HDL particles contain ceramides that cause emphysema in mice; higher HDL-C and HDL-related genes are associated with radiographic emphysema and lower lung function. Aims: To test associations of HDL-C with de...