Please take a moment to review and comment on the measures for sickle cell disease (SCD) research related to Cardiovascular, Pulmonary, and Renal complications proposed for the
PhenX Toolkit. We welcome your feedback on this important initiative.
There are three sickle cell disease (SCD) Working Groups (WG), each covering different aspects of SCD. The first wave (outreach closed) includes SCD measures relevant to Neurology,
Quality of Life, and Health Services. The second wave (outreach now) includes measures relevant to Cardiovascular, Pulmonary, and Renal complications of SCD. The third wave
(outreach in late-June) will include a core set of measures recommended for use by all SCD researchers.
The PhenX (consensus measures for Phenotypes and eXposures) Toolkit
( www.phenxtoolkit.org
) provides investigators with access to well-established, low burden, standardized measures to incorporate into new or existing biomedical studies involving human subjects. The goal of the Toolkit is to encourage use of standard measures that will help researchers collaborate and share data more effectively.
The 16 measures proposed by the PhenX Sickle Cell Disease Cardiovascular, Pulmonary, and
Renal Working Group (WG) are shown in the table below. A limited number of the measures in this table can be added to the PhenX Toolkit, and the Working Group requests your feedback to help guide decisions. The measures currently in the PhenX Toolkit relevant for sickle cell disease research related to Cardiovascular, Pulmonary, and Renal complications are listed after the table.
Dr. Elizabeth Klings, WG Chair, Boston University School of Medicine, thanks you on behalf of the Sickle
Cell Disease Cardiovascular, Pulmonary, and Renal WG.
The Working Group also needs your help identifying protocols and references for the following potential measures: a.
Right Heart Catheterization (RHC) b. Body temperature
For each measure, put a Y in the last column if the measure is useful or an N if the measure is not useful. You may also respond with general comments. Please email your response to feedback@phenx.org
by June 5, 2015. (Collected responses are confidential. E-mail addresses
are not shared or used for any other purpose.)
To review measure details, please click this link: Sickle Cell Disease Working Group Measures for Review

Please Review:
Measure
1. Sleep Disordered
Breathing
2. Chest X-ray
Description of Measurement Protocol
The American Academy of Sleep Medicine (AASM) “Manual for the
Scoring of Sleep and Associated Events: Rules, Terminology and
Technical Specifications” provides instructions for performing and evaluating polysomnograms (PSGs). It contains details regarding electrode placements, standard montages, and digitization parameters, as well as instructions for scoring sleep stages, arousals, movements during sleep, respiratory events during sleep, and cardiac events. The manual is designed to be administered by physicians and technologists who score sleep studies.
The manual is a proprietary online publication that is available for a fee at the AASM website: http://www.aasmnet.org/scoringmanual/ .
In addition to the manual, the AASM website provides practice parameters regarding respiratory indications for PSG in children.
The American College of Radiology - Society for Pediatric Radiology
(ACR-SPR) “Practice Parameter for the Performance of Chest
Radiography” Amended 2014 (Resolution 39) outlines principles for performing high-quality chest X-rays in adult and pediatric participants.
Topics covered include indications and contraindications for chest X-ray, qualifications and responsibilities of personnel, specifications of the examination, documentation and reporting, equipment specifications, radiation safety in imaging, quality control and improvement, safety, infection control, and patient education.
Respond
Here:
Y/N
3. Lung Function –
Diffusion Capacity
The American Thoracic Society (ATS) and the European Respiratory
Society (ERS) Task Force recommendations for standardisation of the single-breath determination of carbon monoxide uptake in the lung outlines principles for performing high-quality single-breath carbon monoxide diffusing capacity (D
L
CO) testing. Topics covered include necessary equipment (e.g., gas analyzers), standardization issues associated with single-breath testing technique, and how to evaluate the quality of measurements of D
L
CO, calculations, definitions and abbreviations.
These recommendations for the single-breath determination of carbon monoxide uptake in the lung are part of a series of recommendations by the ATS/ERS Task Force for the standardization of lung function testing, which can be found on the ATS website at http://www.thoracic.org/statements/pulmonary-function.php
. Detailed information regarding patient preparation is included in the general considerations section of the recommendations for lung function testing in this series.
4. Lung Function – The American Thoracic Society (ATS) and the European Respiratory

Lung Volume Society (ERS) Task Force recommendations for standardisation of the measurement of lung volume testing outline how to obtain measurement of functional residual capacity (FRC) using body plethysmography, nitrogen washout, helium dilution, and imaging techniques. In addition, this source contains details regarding the assessment of total lung capacity (TLC), vital capacity (VC), reserve volume (RV), expiratory reserve volume (ERV), and inspiratory capacity
(IC).
These recommendations for standardization of the measurement of lung volume testing are part of a series of recommendations by the
ATS/ERS Task Force for the standardization of lung function testing, which can be found on the ATS website at http://www.thoracic.org/statements/pulmonary-function.php
. Detailed information regarding patient preparation is included in the general considerations document for lung function testing in this series.
5. N-terminal-probrain natriuretic peptide (NT-pro-
BNP)
This protocol provides instructions for drawing, processing, and storing blood according to the National Health and Nutrition Examination
Survey (NHANES) methods. Because there are many comparable assays for ascertaining levels of N-terminal-pro-brain natriuretic peptide (NTproBNP), the protocol also provides basic guidelines to aid comparability among different studies.
This protocol provides instructions for drawing, processing and storing blood according to the National Health and Nutrition Examination
6. Reticulocyte Count Survey (NHANES) methods. Because there are many comparable assays and instruments for measuring reticulocyte count, the protocol also provides basic guidelines to aid comparability among different studies.
7. Cell Free
Hemoglobin Level
8. Haptoglobin Level
This protocol provides instructions for drawing, processing, and storing blood according to the National Health and Nutrition Examination
Survey (NHANES) methods. Because there are many comparable assays for measuring cell free hemoglobin levels, the protocol also provides basic guidelines to aid comparability among different studies.
This protocol provides instructions for drawing, processing, and storing blood according to the National Health and Nutrition Examination
Survey (NHANES) methods. Because there are many comparable assays for measuring haptoglobin, the protocol also provides basic guidelines to aid comparability among different studies.
9. Bilirubin Level
This protocol provides instructions for drawing, processing, and storing blood according to the National Health and Nutrition Examination
Survey (NHANES) methods. Because there are many comparable assays for measuring bilirubin, the protocol also provides basic guidelines to aid comparability among different studies.
10. Lactate
Dehydrogenase Level
This protocol provides instructions for drawing, processing, and storing blood according to the National Health and Nutrition Examination
Survey (NHANES) methods. Because there are many comparable assays

11. Red Blood Cell
Microparticles Level
12. Red Blood Cell
Aspartate
Aminotransferase
Level for measuring lactate dehydrogenase, the protocol also provides basic guidelines to aid comparability among different studies.
This protocol provides instructions for drawing, processing, and storing blood according to the National Health and Nutrition Examination
Survey (NHANES) methods. Because there are many comparable assays for measuring red blood cell microparticle levels, the protocol also provides basic guidelines to aid comparability among different studies.
This protocol provides instructions for drawing, processing and storing blood according to the National Health and Nutrition Examination
Survey (NHANES) methods. Because there are many comparable assays for measuring red blood cell aspartate aminotransferase (AST), the protocol also provides basic guidelines to aid comparability among different studies.
13. Serum or Plasma
Ferritin
The National Health and Nutrition Examination Survey (NHANES) 2009-
2010 Laboratory Procedures Manual for serum/plasma ferritin testing provides comprehensive instructions for processing and storing blood samples to determine an individual’s serum ferritin level. Because there are many comparable assays and instruments for measuring ferritin, the protocol also provides basic guidelines to aid comparability among different studies.
14. Brachial Artery
Relaxivity ^
15. Liver Iron ^
16. Assessment of
Short-Axis Cardiac
Function by MRI ^
Flow-mediated dilation (FMD) of the brachial artery is a high-frequency ultrasound method to obtain imaging of the brachial artery to assess endothelial function. Endothelial function has been associated as a factor in the pathology of various medical conditions, such as congestive heart failure, atherosclerosis, and hypertension.
This protocol includes a brief background describing how magnetic resonance imaging (MRI) is used to determine the concentration of iron in the liver and provides references for quantifying liver iron by MRI
R2*.
The American College of Radiology - North American Society for
Cardiovascular Imaging - Society for Pediatric Radiology (ACR-NASCI-
SPR) “Practice Parameter for the Performance and Interpretation of
Cardiac Magnetic Resonance Imaging (MRI)” Amended 2014 (Resolution
39) outlines principles for performing high-quality cardiac MRI in adult and pediatric participants. Topics covered include indications, qualifications and responsibilities of personnel, safety guidelines and possible contraindications, specifications of the examination, documentation, equipment specifications, quality control and improvement, safety, infection control, and patient education.
Right Heart
Catheterization
(RHC)
The SCD WG would appreciate suggestions for protocols to standardize collection of RHC data elements. If you have suggestions,
please list them (and your Y/N response) in the column to the right.
Body Temperature
The SCD WG would appreciate suggestions for protocols to standardize collection of body temperature. If you have suggestions,

please list them (and your Y/N response) in the column to the right.
^
Indicates a supplemental information measure
The PhenX Toolkit already contains the following measures that may be relevant for sickle cell disease research related to Cardiovascular, Pulmonary, and Renal complications:
 Arterial Blood Gas (ABG)
 Bronchodilator Responsiveness (BDR)
 Exercise Capacity/Six-Minute Walk Test

Peak Expiratory Flow Rate (PEFR)
 Personal and Family History of Respiratory Symptoms/Diseases

Sleep Apnea

Pulse Oximetry (Rest)

Pulse Oximetry (Sleep) (Supplemental Information)

Respiratory Rate

Spirometry

Chest Computed Tomography (CT)

Heart Valve Function (contains echocardiogram)

Abdominal Aortic Aneurysm
 Blood Pressure (Adult/Primary)
 Deep Venous Thrombosis
 History of Stroke - Ischemic Infarction and Hemorrhage
 Peripheral Arterial Disease
 Pulmonary Embolism

Liver Function Assay
 Migraine

Pain, Abdominal (Type and Intensity)

Personal History of Kidney Failure

Serum Creatinine Assay for Kidney Function

Urinary Creatinine Assay for Kidney Function

Urinary Microalbumin Assay for Kidney Function

Cystatin C Assay for Kidney Function (Supplemental Information)
PhenX Measures for Sickle Cell Disease (SCD) Research Project
The PhenX Measures for Sickle Cell Disease (SCD) Research project is funded by the National
Heart, Lung, and Blood Institute (Ellen Werner, Project Scientist) and the National Human
Genome Research Institute (Erin Ramos, Project Scientist), and led by RTI International (Carol
Hamilton, Principle Investigator). The overall direction and guidance to the PhenX Measures for the Sickle Cell Disease Research Project is provided by the Sickle Cell Disease Research and
Scientific Panel (SRSP), co-chaired by James Eckman and Kathryn Hassell.

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