David A. Kaminsky

University of Vermont

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Charles G. Irvin

University of Vermont

Anne E. Dixon

University of Vermont

Jason H. T. Bates

University of Vermont

Robert A. Wise

Johns Hopkins University

Meredith C. McCormack

Johns Hopkins University

Sanja Stanojevic

Dalhousie University

Ubong Peters

Roche (United States)

Jeffrey M Haynes

Elliot Hospital

Janet T. Holbrook

Johns Hopkins University

Martha B. Pitman

Harvard University

Cooperative Institutions

University of Vermont

408

Massachusetts General Hospital

391

Virginia Commonwealth University

287

Mount Sinai Hospital

229

John Wiley & Sons (United States)

165

The University of Texas MD Anderson Cancer Center

156

Università Cattolica del Sacro Cuore

136

Hudson Institute

119

Harvard University

115

Johns Hopkins University

113

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Relationship between the baseline alveolar volume‐to‐total lung capacity ratio and airway responsiveness

Respirology (2014)

David A. Kaminsky Anees Daud David G. Chapman

Abstract Background and objective Ventilation heterogeneity ( VH ) has been linked to airway responsiveness ( AR ) based on various measures of VH involving inert gas washout, forced oscillation and lung imaging. We explore whether VH at baseline, as measured by the simple ratio of single breath alveolar volume to plethysmographically determined total lung capacity ( VA / TLC ), would correlate with AR as measured by methacholine challenge testing. Methods We analysed data from spirometry, lung volumes, diffusing capacity and methacholine challenge to derive the VA / TLC and the dose–response slope ( DRS ) of forced expiratory volume in 1 s ( DRS ‐ FEV 1) during methacholine challenge from 136 patients. We separated out airway closure versus narrowing by examining the DRS for forced vital capacity ( DRS‐FVC ) and the DRS for FEV 1/ FVC ( DRS ‐ FEV 1/ FVC ), respectively. Similarly, we calculated the DRS for s G aw ( DRS ‐s G aw) as another measure of airway narrowing. We performed statistical analysis using Spearman rank correlation and multifactor linear regression using a backward stepwise modelling procedure. Results We found that the DRS ‐ FEV 1 correlated with baseline VA / TLC (rho = −0.26, P < 0.01), and VA / TLC and FEV 1 were independently associated with DRS ‐ FEV 1 (R 2 = 0.14, P = 0.01). In addition, VA / TLC was associated with both airway narrowing and closure in response to methacholine. Conclusions These results confirm that baseline VA / TLC is associated with AR , and reflects both airway closure and airway narrowing following methacholine challenge.

Methacholine

Vital capacity

10.1111/resp.12347

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Citations (16)

Peripheral Lung Responsiveness Assessed by Forced Oscillations Through the Wedged Bronchoscope

CHEST Journal (2003)

David A. Kaminsky C. G. Irvin Henrique Takachi Moriya Mary Lynn Sherburn Lang

Methacholine

10.1378/chest.123.3_suppl.363s

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Citations (10)

Methacholine challenge test: Diagnostic characteristics in asthmatic patients receiving controller medications

Journal of Allergy and Clinical Immunology (2012)

Kaharu Sumino Elizabeth A. Sugar Charles G. Irvin David A. Kaminsky Dave Shade

Methacholine

Atopy

Bronchial hyperresponsiveness

Airway hyperresponsiveness

10.1016/j.jaci.2012.02.025

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Citations (80)

Peripheral lung mechanics in asthma: Exploring the outer limits

Pulmonary Pharmacology & Therapeutics (2010)

David A. Kaminsky

Respiratory physiology

Airway obstruction

10.1016/j.pupt.2010.12.001

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Citations (15)

Influence of distinct asthma phenotypes on lung function following weight loss in the obese

Respirology (2014)

David G. Chapman Charles G. Irvin David A. Kaminsky Patrick Forgione Jason H. T. Bates

Abstract Background and objective There appears to be two distinct clinical phenotypes of obese patients with asthma—those with early‐onset asthma and high serum IgE ( T H 2 ‐high), and those with late‐onset asthma and low serum IgE ( T H 2 ‐low). The aim of the present study was to determine in the two phenotypes of obese asthma the effect of weight loss on small airway function. Methods T H 2 ‐low ( n = 8) and T H 2 ‐high ( n = 5) obese asthmatics underwent methacholine challenge before and 12 months following bariatric surgery. Dose–response slopes as measures of sensitivity to airway closure and narrowing were measured as maximum % fall forced vital capacity ( FVC ) and forced expiratory volume in 1 s/ FVC , respectively, divided by dose. Resting airway mechanics were measured by forced oscillation technique. Results Weight loss reduced sensitivity to airway closure in T H 2 ‐low but not T H 2 ‐high obese asthmatics (pre‐post mean change ± 95% confidence interval: 1.8 ± 0.8 doubling doses vs −0.3 ± 1.7 doubling doses, P = 0.04). However, there was no effect of weight loss on the sensitivity to airway narrowing in either group ( P = 0.8, T H 2 ‐low: 0.8 ± 1.0 doubling doses, T H 2 ‐high: −1.1 ± 2.5 doubling doses). In contrast, respiratory resistance (20 Hz) improved in T H 2 ‐high but not in T H 2 ‐low obese asthmatics (pre‐post change median interquartile range: 1.5 (1.3–2.8) cmH 2 O /L/s vs 0.6 (−1.8–0.8) cmH 2 O /L/s, P = 0.03). Conclusions T H 2 ‐low obese asthmatics appear to be characterized by increased small airway responsiveness and abnormalities in resting airway function that may persist following weight loss. However, this was not the case for T H 2 ‐high obese asthmatics, highlighting the complex interplay between IgE status and asthma pathophysiology in obesity.

Methacholine

Interquartile range

Vital capacity

10.1111/resp.12368

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Citations (65)

Is There a Role for Using Race-Specific Reference Equations? Yes and No

American Journal of Respiratory and Critical Care Medicine (2022)

David A. Kaminsky

10.1164/rccm.202201-0006ed

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Citations (9)

SARS-CoV-2 hijacks host cell genome instability pathways

Research Square (Research Square) (2022)

Joshua Victor Tristan X. Jordan Erica N. Lamkin Kanayo Ikeh Anthony March

Abstract The repertoire of coronavirus disease 2019 (COVID-19)-mediated adverse health outcomes has continued to expand in infected patients, including the susceptibility to developing long-COVID; however, the molecular underpinnings at the cellular level are poorly defined. In this study, we report that SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection triggers host cell genome instability by modulating the expression of molecules of DNA repair and mutagenic translesion synthesis. Further, SARS-CoV-2 infection causes genetic alterations, such as increased mutagenesis, telomere dysregulation, and elevated microsatellite instability (MSI). The MSI phenotype was coupled to reduced MLH1, MSH6, and MSH2 in infected cells. Strikingly, pre-treatment of cells with the REV1-targeting translesion DNA synthesis inhibitor, JH-RE-06, suppresses SARS-CoV-2 proliferation and dramatically represses the SARS-CoV-2-dependent genome instability. Mechanistically, JH-RE-06 treatment induces autophagy, which we hypothesize limits SARS-CoV-2 proliferation and, therefore, the hijacking of host-cell genome instability pathways. These results have implications for understanding the pathobiological consequences of COVID-19.

Microsatellite Instability

Coronavirus

10.21203/rs.3.rs-1556634/v1

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Citations (7)

Diagnosis of a space-occupying lesion of the lung by pulmonary function tests.

PubMed (2003)

Suzanne Redden Deborah A Hunton David A. Kaminsky

Source

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A Race-neutral Approach to the Interpretation of Lung Function Measurements

American Journal of Respiratory and Critical Care Medicine (2022)

Cole Bowerman Nirav R. Bhakta Danny J. Brazzale Brendan R. Cooper Julie Cooper

Rationale: The use of self-reported race and ethnicity to interpret lung function measurements has historically assumed that the observed differences in lung function between racial and ethnic groups were because of thoracic cavity size differences relative to standing height. Very few studies have considered the influence of environmental and social determinants on pulmonary function. Consequently, the use of race and ethnicity-specific reference equations may further marginalize disadvantaged populations. Objectives: To develop a race-neutral reference equation for spirometry interpretation. Methods: National Health and Nutrition Examination Survey (NHANES) III data (n = 6,984) were reanalyzed with sitting height and the Cormic index to investigate whether body proportions were better predictors of lung function than race and ethnicity. Furthermore, the original GLI (Global Lung Function Initiative) data (n = 74,185) were reanalyzed with inverse-probability weights to create race-neutral GLI global (2022) equations. Measurements and Main Results: The inclusion of sitting height slightly improved the statistical precision of reference equations compared with using standing height alone but did not explain observed differences in spirometry between the NHANES III race and ethnic groups. GLI global (2022) equations, which do not require the selection of race and ethnicity, had a similar fit to the GLI 2012 “other” equations and wider limits of normal. Conclusions: The use of a single global spirometry equation reflects the wide range of lung function observed within and between populations. Given the inherent limitations of any reference equation, the use of GLI global equations to interpret spirometry requires careful consideration of an individual’s symptoms and medical history when used to make clinical, employment, and insurance decisions.

10.1164/rccm.202205-0963oc

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Citations (120)

RADON AWARENESS AND MITIGATION IN VERMONT: A PUBLIC HEALTH SURVEY

Health Physics (2007)

Erik Riesenfeld Theodore W. Marcy Kyndaron Reinier Joan A. Mongeon Craig W. Trumbo

Radon exposure is associated with an increased incidence of lung cancer, and elevated levels may be found in as many as 1 out of 15 homes. The U.S. EPA recommends testing homes for radon and mitigating over the advisory level of 4 picocuries per liter (4 pCi L(-1), or 148 Bq m(-3)). A sample population from a list of Vermont residents who had tested their residence for radon through the Vermont Department of Health and who had elevated levels were mailed a survey to assess demographic characteristics, knowledge about radon, mitigation rates, types of mitigation, as well as barriers to mitigation. The response rate was 63%. Forty-three percent of respondents mitigated. Roughly half were not completely knowledgeable of radon based upon the ability to associate radon exposure with lung cancer risk. Reasons not to mitigate radon levels in homes were cost and lack of concern over elevated levels. A multivariate logistic regression analysis revealed factors associated with mitigating: an education level of college or higher (p = 0.02), concern that a high radon level would affect real estate value (p = 0.04), and home age less than 10 y (p = 0.05). In summary, less than half of Vermonters with elevated radon levels participating in the Department of Health program mitigated. We identify factors associated with radon mitigation that may lead to improved radon education and mitigation practice.

10.1097/01.hp.0000254862.50407.4a

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Citations (19)