Publications by authors named "Aparna Balasubramanian"

9 Publications

  • Page 1 of 1

Haemoglobin as a biomarker for clinical outcomes in chronic obstructive pulmonary disease.

ERJ Open Res 2021 Jul 26;7(3). Epub 2021 Jul 26.

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.

In COPD, anaemia is associated with increased morbidity, but the relationship between haemoglobin over its entire observed range and morbidity is poorly understood. Such an understanding could guide future therapeutic targeting of haemoglobin in COPD management. Leveraging the COPDGene study, we conducted a cross-sectional analysis of haemoglobin from COPD participants, examining symptoms, quality of life, functional performance, and acute exacerbations of COPD (AECOPD). Haemoglobin was analysed both as a continuous variable and categorised into anaemia, normal haemoglobin, and polycythaemia groups. Fractional polynomial modelling was used for continuous analyses; categorical models were multivariable linear or negative binomial regressions. Covariates included demographics, comorbidities, emphysema, diffusing capacity, and airflow obstruction. From 2539 participants, 366 (14%) were identified as anaemic and 125 (5%) as polycythaemic. Compared with normal haemoglobin, anaemia was significantly associated with increased symptoms (COPD Assessment Test score: p=0.006, modified Medical Research Council (mMRC) Dyspnoea Score: p=0.001); worse quality of life (St. George's Respiratory Questionnaire (SGRQ) score: p<0.001; Medical Outcomes Study Short Form 36-item Questionnaire (SF-36) General Health: p=0.002; SF-36 Physical Health: p<0.001), decreased functional performance (6-min walk distance (6MWD): p<0.001), and severe AECOPD (p=0.01), while polycythaemia was not. Continuous models, however, demonstrated increased morbidity at both ends of the haemoglobin distribution (p<0.01 for mMRC, SGRQ, SF-36 Physical Health, 6MWD, and severe AECOPD). Evaluating interactions, both diffusing capacity and haemoglobin were independently associated with morbidity. We present novel findings that haemoglobin derangements towards either extreme of the observed range are associated with increased morbidity in COPD. Further investigation is necessary to determine whether haemoglobin derangement drives morbidity or merely reflects systemic inflammation, and whether correcting haemoglobin towards the normal range improves morbidity.
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http://dx.doi.org/10.1183/23120541.00068-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311135PMC
July 2021

A novel approach to perioperative risk assessment for patients with pulmonary hypertension.

ERJ Open Res 2021 Jul 19;7(3). Epub 2021 Jul 19.

Dept of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.

Rationale: Pulmonary hypertension (PH) is associated with significant perioperative morbidity and mortality. We hypothesised that pulmonary arterial hypertension (PAH) composite risk assessment scores could estimate perioperative risk for PH patients when adjusted for inherent procedural risk.

Methods: We identified patients in the Johns Hopkins PH Center Registry that had noncardiac surgery (including endoscopies) between September 2015 and January 2020. We collected information on preoperative patient-level and procedural variables and used logistic regression to evaluate associations with a composite outcome of death within 30 days or serious postoperative complication. We generated composite patient-level risk assessment scores for each subject and used logistic regression to estimate the association with adverse surgical outcomes. We adjusted multivariable models for inherent procedural risk of major cardiovascular events and used these models to generate a numerical PH perioperative risk (PHPR) score.

Results: Among 150 subjects, 19 (12.7%) reached the primary outcome, including 7 deaths (4.7%). Individual patient-level and procedural variables were associated with the primary outcome (all p<0.05). A composite patient-level risk assessment score built on three noninvasive parameters was strongly associated with reduced risk for poor outcomes (OR=0.4, p=0.03). This association was strengthened after adjusting the model for procedural risk. A PHPR score derived from the multivariable model stratified patients into low (0%), intermediate (≤10%), or high (>10%) risk of reaching the primary outcome.

Conclusion: Composite PAH risk assessment scores can predict perioperative risk for PH patients after accounting for inherent procedural risk. Validation of the PHPR score in a multicentre, prospective cohort is warranted.
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http://dx.doi.org/10.1183/23120541.00257-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287131PMC
July 2021

Polycythemia is Associated with Lower Incidence of Severe COPD Exacerbations in the SPIROMICS Study.

Chronic Obstr Pulm Dis 2021 Jul;8(3):326-335

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, United States.

Secondary polycythemia has long been recognized as a consequence of chronic pulmonary disease and hypoxemia and is associated with lower mortality and fewer hospitalizations among individuals with chronic obstructive pulmonary disease (COPD)-prescribed long-term oxygen therapy. This study investigates the association of polycythemia with COPD severity, phenotypic features, and respiratory exacerbations in a contemporary and representative sample of individuals with COPD. Current and former smokers with COPD (forced expiratory volume in 1 second [FEV] to forced vital capacity [FVC] ratio <70%) without a history of hematologic/oncologic disorders were selected from the SubPopulations and InteRmediate Outcomes Measures In COPD Study (SPIROMICS), a multi-center observational cohort. Participants with polycythemia (hemoglobin ≥15g/dL [females] or ≥17g/dL [males]), were compared to individuals without anemia (hemoglobin ≥12g/dL [females] or ≥13g/dL [males]). Cross-sectional outcomes including percent predicted FEV, respiratory symptoms, quality of life, exercise tolerance, and percentage and distribution of emphysema (voxels<-950 Hounsfield units [HU] at total lung capacity) were evaluated using linear or logistic regression. Longitudinal acute exacerbation of COPD (AECOPD) and severe AECOPD (requiring an emergency department visit or hospitalization) were assessed using zero-inflated negative binomial models. Among 1261 participants, 148 (11.7%) had polycythemia. Average follow-up was 4.2±1.7 years and did not differ by presence of polycythemia. In multivariate analysis, compared to participants with normal hemoglobin, polycythemia was associated with a reduced rate of severe AECOPD (adjusted incidence rate ratio 0.57, 95% CI: 0.33-0.98), lower percent predicted FEV, lower resting oxygen saturation, increased upper to lower lobe ratio of emphysema, and a greater degree of emphysema, though the latter was attenuated after adjusting for lung function. There were no significant differences in total AECOPD, patient-reported outcomes, or exercise tolerance. These findings suggest that polycythemia, while associated with less favorable physiologic parameters, is not independently associated with symptoms, and is associated with fewer severe exacerbations. Future studies should explore the potentially protective role of increased hemoglobin beyond the correction of anemia.
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http://dx.doi.org/10.15326/jcopdf.2021.0216DOI Listing
July 2021

Burden and Unmet Needs with Portable Oxygen in Patients on Long-Term Oxygen Therapy.

Ann Am Thorac Soc 2021 Sep;18(9):1498-1505

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins School of Medicine, and.

Over 1.5 million Americans receive long-term oxygen therapy (LTOT) for the treatment of chronic hypoxemia to optimize functional status and quality of life. However, current portable oxygen equipment, including portable gas tanks (GTs), portable liquid tanks (LTs), and portable oxygen concentrators (POCs), each have limitations that can hinder patient mobility and daily activities. To examine patient experiences with portable oxygen to guide equipment innovation and thereby improve patient care on oxygen therapy. The burden and unmet needs with portable oxygen equipment were assessed in 836 LTOT patients with chronic lung disease (chronic obstructive pulmonary disease [COPD], interstitial lung disease, and pulmonary hypertension) through an online survey. The survey included a combination of multiple-choice, Likert-scale, short-answer, and open-ended questions. Distribution was achieved through patient support organizations, including the U.S. COPD Coalition, the Pulmonary Fibrosis Foundation, and the Pulmonary Hypertension Association. Improvements in portability were ranked as the highest priority by patients across all equipment types, followed by increases in the duration of oxygen supply for GTs, accessibility for LTs, and flow capabilities for POCs. All device types were found to be burdensome, with the greatest burden among GT users, 51% of whom characterized GT use as "strenuous" or "extremely strenuous" (high burden). POCs ranked as the most common (61%) and least burdensome devices; however, 29% of POC users still reported a high associated burden. Forty-seven percent of POC respondents described using a POC despite it not meeting their oxygen needs to benefit from advantages over alternative equipment. Among non-POC users, limited oxygen flow rate capabilities and cost were the top reasons preventing POC use. Although improvements have been made to portable oxygen equipment, this study highlights the burden that remains and reveals a clear need for advances in technology to improve the functional status and quality of life of portable LTOT users.
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http://dx.doi.org/10.1513/AnnalsATS.202005-487OCDOI Listing
September 2021

Diffusing Capacity Is an Independent Predictor of Outcomes in Pulmonary Hypertension Associated With COPD.

Chest 2020 08 14;158(2):722-734. Epub 2020 Mar 14.

Johns Hopkins University Division of Pulmonary and Critical Care, Baltimore, MD. Electronic address:

Background: Patients with COPD who experience pulmonary hypertension (PH) have worse mortality than those with COPD alone. Predictors of poor outcomes in COPD-PH are not well-described. Diffusing capacity of the lung (Dlco) assesses the integrity of the alveolar-capillary interface and thus may be a useful prognostic tool among those with COPD-PH.

Research Question: Using a single center registry, we sought to evaluate Dlco as a predictor of mortality in a cohort of patients with COPD-PH.

Study Design And Methods: This retrospective cohort study analyzed 71 COPD-PH patients from the Johns Hopkins Pulmonary Hypertension Registry with right-sided heart catheterization (RHC)-proven PH and pulmonary function testing data within one year of diagnostic RHC. Transplant-free survival was calculated from index RHC. Adjusted transplant-free survival was modelled using Cox proportional hazard methods; age, pulmonary vascular resistance, FEV, oxygen use, and N-terminal pro-brain natriuretic peptide were included as covariates.

Results: Overall unadjusted transplant-free 1-, 3-, and 5-year survivals were 87%, 60%, and 51%, respectively. Survival was associated with reduced Dlco across the observed range of pulmonary artery pressures and pulmonary vascular resistance. Severe Dlco impairment was associated with poorer survival (log-rank χ 13.07) (P < .001); adjusting for covariates, for every percent predicted decrease in Dlco, mortality rates increased by 4% (hazard ratio, 1.04; 95% CI, 1.01-1.07).

Interpretation: Among patients with COPD-PH, severe gas transfer impairment is associated with higher mortality, even with adjustment for airflow obstruction and hemodynamics, which suggests that Dlco may be a useful prognostic marker in this population. Future studies are needed to further investigate the association between Dlco and morbidity and to determine the utility of Dlco as a biomarker for disease risk and severity in COPD-PH.
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http://dx.doi.org/10.1016/j.chest.2020.02.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173778PMC
August 2020

Diffusing Capacity of Carbon Monoxide in Assessment of COPD.

Chest 2019 12 25;156(6):1111-1119. Epub 2019 Jul 25.

Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD. Electronic address:

Background: Diffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown.

Objective: The goal of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging.

Methods: Data for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV percent predicted among other confounders.

Results: In multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 [P < .001]; St. George's Respiratory Questionnaire, 1.67 [P < .001]; Medical Outcomes Study Short Form 36 Physical Function, -0.89 [P < .001]), exercise performance (6-min walk distance, -45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV alone, or both Dlco and FEV were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes).

Conclusions: Impairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.
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http://dx.doi.org/10.1016/j.chest.2019.06.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242635PMC
December 2019

Non-Cystic Fibrosis Bronchiectasis: Microbiology, Clinical Outcomes, and Pharmacotherapy Practices.

Am J Respir Crit Care Med 2019 Mar;199(5):651-653

1 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.

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http://dx.doi.org/10.1164/rccm.201805-0848RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396858PMC
March 2019

Restrictive Spirometry and Cardiovascular Risk: Cause or Comorbidity?

Ann Am Thorac Soc 2018 10;15(10):1142-1143

1 Johns Hopkins University School of Medicine Baltimore, Maryland.

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http://dx.doi.org/10.1513/AnnalsATS.201807-494EDDOI Listing
October 2018
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