Table of Contents

Component Description

The measurement of fractional exhaled nitric oxide (FENO) was one of two NHANES 2011-12 examination components on respiratory health sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Spirometry, including a 2nd test post-bronchodilator spirometry exam, was also conducted. Nitric Oxide (NO) is a chemical normally produced in the respiratory tract and can be detected in the exhaled breath. It is a noninvasive marker of airway inflammation. FENO has been shown to be higher in persons with asthma, chronic obstructive pulmonary disease (COPD) and other respiratory conditions as compared to levels found in healthy persons. FENO measurements have also been used as a tool to monitor compliance with treatment with inhaled steroids in asthmatics.

The objective of the nitric oxide exam was to produce baseline FENO measurements and reference ranges for the U.S. healthy population as well as those with asthma and COPD, and those who are smokers. The data collection was also intended to help define the prevalence of undiagnosed airway inflammation in the US, and to examine the association between airway inflammation, other measurements of lung function and capacity, and physical and laboratory measures.

 

Eligible Sample

Survey participants, aged 6 to 79 years, were eligible for FENO testing. Participants that had current chest pain or a physical problem with forceful expiration, or those who were using supplemental oxygen were medically-excluded from participating.

 

Protocol and Procedure

FENO was measured using the Aerocrine NIOX MINO®, a portable, hand-held NO analyzer (Aerocrine AB, Solna, Sweden) approved by the FDA in 2008. This device relies on an electrochemical sensor to detect exhaled NO levels and provides measurements of from 5 to 300 ppb in whole numbers. The testing was conducted with participants sitting in front of a mirror so they could see display prompts on the NO analyzer screen. Holding the device, participants were asked to first empty their lungs, then to place their mouth on the disposable analyzer's filter mouthpiece, and to fill their lungs to capacity with NO-free air. Participants were then asked to blow out all of their air at a constant pressure while exhaled NO from the bronchial tree was measured. The NIOX MINO® has a dynamic flow restrictor to stabilize flow rate at 50 ml/sec. The device automatically provides auditory and visual cues to assist in performing the test correctly. The health technicians also coach participants to maintain the air flow at a slow, fixed, steady rate. The standard exhalation time, as specified by the manufacturer, was 10 seconds for participants who were at or above 130 cm in height, and 6 seconds for those below 130 cm. The Respiratory Health ENO Procedures Manual provides detailed description of the examination procedure. The manual is available at : https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/default.aspx?BeginYear=2007

The test result, an integer between 5-300 ppb, was displayed on the screen of the device 140 seconds after a valid test was completed. Codes indicating a result either above or below the range of the device detection limit, as well as error codes, were also displayed on the screen. It was common for current smokers to have repeat FENO levels below the limit of detection. Results indicating a value above the limit of detection were unusual, and subsequent measurements were often within the normal range of the test device.

The NHANES protocol required two FENO measurements that were reproducible, in accordance with testing procedures recommended by the manufacturer and similar to those published by the American Thoracic Society and European Respiratory Society. If either or both of the first two valid FENO measurements was below 30 ppb and the measurements were within 2 ppb of each other, or if both measurements were over 30 ppb and within 10% of each other, then the test was considered reproducible and complete. Two values below the limit of detection or above the limit of detection were also considered reproducible. If the reproducibility criteria were not met within the first two exhalations, a participant had 2 additional exhalations to satisfy the criteria (up to a total of 4 trials). The participant’s exhalations for which the NIOX MINO® did not display a valid reading, i.e., exhalations that were either too strong or too weak, or any other reasons for failing to achieve a successful exhalation were recorded as attempts. Examinees were not always able to meet the criteria for a reproducible measurement even within the ten attempts allowed to perform the exhalation, as indicated by the exam status variable ENXSTAT.

 

Quality Assurance & Quality Control

The chief Health Technician, at each MEC, monitored ongoing staff performance in the field. Health technician performance was also monitored using direct observation during periodic site visits. The NIOX MINO® monitor was cleaned and calibrated in accordance with the requirements via regularly scheduled quality control checks by the Health Technicians and verified by supervisory staff. Ambient air testing was conducted daily, and temperature and humidity collection in the respiratory health room was ongoing. A QC sensor verification was conducted at FENO levels of 15 and 75 ppb and QC filter checks were also conducted to check a “blank sample” at 0 ppb. Each pre-calibrated NIOX MINO® sensor has a maximum of 300 measurements and sensors were replaced in the device when 30 measurements remained. The sensor shelf life is 1 year from the date of manufacture, and the device shelf life is 3.5 years from the date of manufacture, or up to 1500 uses. The Respiratory Health ENO Procedures Manual provides detailed descriptions of the quality assurance and quality control measures that were used over the course of the 2011-2012 data collection period.

All used sensors were returned to the manufacturer (Aerocrine AB, Sweden) to determine if the sensors maintained the initial test specification quality control criteria. Results from these checks were provided to NCHS for review. During the 2011-12 testing period, all sensors satisfied the quality control calibration criteria.

 

Data Processing and Editing

Edits were made to ensure completeness, consistency and analytic usefulness of the data.

 

Analytic Notes

Screening Questions ENQ040–ENQ100: A series of questions that varied by age were administered in the examination to support data analysis and interpretation. Participants 12 years and older were asked the questions while waiting for the test results after the first acceptable exhalation. Parents of youth 6-11 years were asked these questions, as well as the two medical exclusion questions (ENQ010 and ENQ020) prior to the exam.

Exhaled NO Status Code (ENXSTAT): This single variable provides a completion code for the component:

1: Two measurements met the reproducibility criteria (as described in the Protocol/Procedures section of this document). Only examinees with this status code have a calculated mean FENO value (ENXMEAN).
2: At least one acceptable measurement was obtained. For those with two or more measurements, results were not reproducible.
3: Unable to perform test. Attempted the exhalation up to 10 times but were not successful in achieving a measurement.
4: Medically excluded. Responded positively to or did not answer one of two exclusion questions (ENQ010, ENQ020) prior to the test.
5: Test was not conducted for reason described in ENXCMT.

ENXTR1G, ENXTR2G, ENXTR3G, ENXTR4G: These variables indicate a trial status, respectively, for each of the valid FENO readings that were obtained; i.e., whether an exhalation produced a measurement that was within range of the acceptable device specifications (5-300 ppb), or whether it was either above or below the instrument's limit of detection. If all attempts were used (up to 10 total, across all trials) or the examinee wished to terminate the exam, then a “could not obtain” response was recorded.
ENXTR1Q, ENXTR2Q, ENXTR3Q, ENXTR4Q: These variables indicate the numeric value for the FENO reading if it fell within the NIOX MINO® measurement range (5-300 ppb). If the trial status indicates that the measurement was not within the range or could not be obtained, then the FENO measurement will be missing.

ENXMEAN: For analytic purposes, this variable was created for the average of two reproducible measurements. Results from up to 4 successful exhalation trials (ENXTR1Q, ENXTR2Q, ENXTR3Q, ENXTR4Q) were used to assess reproducibility, and the two reproducible FENO measurements were averaged to create a mean value (ENXMEAN). Two measurements below the limit of detection of the device (i.e., less than 5 ppb) were also considered reproducible and given a “fill” value of 3.5 ppb. This value was determined using the same calculation applied to the NHANES laboratory data - the limit of detection divided by the square root of two. Two measurements above the limit of detection of the device (i.e., above 300 ppb) were also considered reproducible when auxiliary measurements were found be in the high range. ENXMEAN was given a “fill” value of 301 ppb in these cases. Analysts may choose to use alternate values for FENO levels below or above the limit of detection, or to exclude records with these values from their analyses.

Sample Weights: The NHANES full sample 2-Year MEC Exam Weights (WTMEC2YR) should be used to analyze the 2011-12 FENO data. Please refer to the NHANES Analytic Guidelines (https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx) and the on-line NHANES Tutorial (https://www.cdc.gov/nchs/tutorials/) for further details on the use of sample weights and other analytic issues.

Additional 2011-2012 NHANES Data on Respiratory Health:
The NHANES Respiratory Health Component also included Spirometry (SPX_G) and Household Interview Questionnaire data on a prior diagnosis of asthma and COPD (MCQ_G), recent respiratory symptoms such as cough and wheezing (RDQ_G), and data for the participant's current prescription medications (RXQ_RX_G; RXQ_DRUG_G). In addition raw data for the spirometry curves attempted by each participant is released in a separate dataset (SPXRAW_G).

 

References

Codebook and Frequencies

SEQN - Respondent sequence number

Variable Name:
SEQN
SAS Label:
Respondent sequence number
English Text:
Respondent sequence number
Target:
Both males and females 6 YEARS - 79 YEARS

ENXSTAT - Status code for ENO exam

Variable Name:
ENXSTAT
SAS Label:
Status code for ENO exam
English Text:
Status code for ENO exam
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Two reproducible FENO measurements 6525 6525
2 One or more FENO measurement; not reproducible 117 6642
3 Attempted exam; no FENO measurements 297 6939
4 Medical exclusion; no FENO measurements 109 7048
5 Exam not done; no FENO measurements 447 7495 ENXCMT
. Missing 0 7495

ENXCMT - Comment for ENO exams not done

Variable Name:
ENXCMT
SAS Label:
Comment for ENO exams not done
English Text:
Comment for ENO exams not done
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Safety exclusion 11 11
2 SP refusal 32 43
3 No time 46 89
4 Physical limitation 25 114
5 Communication problem 35 149
6 Equipment failure 8 157
7 SP ill/emergency 14 171
14 Interrupted 1 172
56 Came late/left early 225 397
84 SP with child 33 430
99 Other 17 447
. Missing 7048 7495

ENQ010 - Breathing problem require oxygen?

Variable Name:
ENQ010
SAS Label:
Breathing problem require oxygen?
English Text:
Medical Exclusion Question
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 41 41 End of Section
2 No 7007 7048
7 Refused 0 7048 End of Section
9 Don't know 0 7048 End of Section
. Missing 447 7495

ENQ020 - Problem taking deep breath?

Variable Name:
ENQ020
SAS Label:
Problem taking deep breath?
English Text:
Medical Exclusion Question
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 66 66 End of Section
2 No 6939 7005
7 Refused 0 7005 End of Section
9 Don't know 2 7007 End of Section
. Missing 488 7495

ENQ040 - Smoked last hour?

Variable Name:
ENQ040
SAS Label:
Smoked last hour?
English Text:
Within the last hour have you smoked a cigarette, cigar, pipe , or used any other tobacco product?
Target:
Both males and females 16 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 277 277
2 No 4693 4970
7 Refused 0 4970
9 Don't know 0 4970
. Missing 2525 7495

ENQ050 - Exercised strenuously last hour?

Variable Name:
ENQ050
SAS Label:
Exercised strenuously last hour?
English Text:
[Within the last hour] have you exercised strenuously?
Target:
Both males and females 12 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 54 54
2 No 5501 5555
7 Refused 0 5555
9 Don't know 0 5555
. Missing 1940 7495

ENQ060 - Ate or drink last hour?

Variable Name:
ENQ060
SAS Label:
Ate or drink last hour?
English Text:
[Within the last hour] have you had anything to eat or drink?
Target:
Both males and females 12 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 2997 2997
2 No 2558 5555
7 Refused 0 5555
9 Don't know 0 5555
. Missing 1940 7495

ENQ070 - Ate NO-rich vegetables, 3 hours?

Variable Name:
ENQ070
SAS Label:
Ate NO-rich vegetables, 3 hours?
English Text:
Within the last three hours have you eaten beets, broccoli, cabbage, celery, lettuce, spinach or radishes?
Target:
Both males and females 12 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 238 238
2 No 5317 5555
7 Refused 0 5555
9 Don't know 0 5555
. Missing 1940 7495

ENQ080 - Ate NO-rich rich meats, 3 hours?

Variable Name:
ENQ080
SAS Label:
Ate NO-rich rich meats, 3 hours?
English Text:
Within the last three hours have you eaten bacon, ham, hot dogs or smoked fish?
Target:
Both males and females 12 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 212 212
2 No 5343 5555
7 Refused 0 5555
9 Don't know 0 5555
. Missing 1940 7495

ENQ090 - Used oral or inhaled steroids, 2 days?

Variable Name:
ENQ090
SAS Label:
Used oral or inhaled steroids, 2 days?
English Text:
Within the last two days {have you/has SP} used any oral or inhaled steroids? This list provides some examples
English Instructions:
SHOW HANDCARD
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 266 266
2 No 6373 6639
7 Refused 0 6639
9 Don't know 3 6642
. Missing 853 7495

ENQ100 - Cough, cold, resp illness, 7 days?

Variable Name:
ENQ100
SAS Label:
Cough, cold, resp illness, 7 days?
English Text:
In the past 7 days, {have you/has SP} had a cough, cold, phlegm, runny nose or other respiratory illness? Do not count allergies or hay fever
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Yes 1259 1259
2 No 5379 6638
7 Refused 0 6638
9 Don't know 4 6642
. Missing 853 7495

ENAATMPT - Total number of exhalation attempts

Variable Name:
ENAATMPT
SAS Label:
Total number of exhalation attempts
English Text:
Enter total number of attempts
English Instructions:
ENTER TOTAL NUMBER OF ENO ATTEMPTS
Target:
Both males and females 6 YEARS - 79 YEARS
Hard Edits:
1 to 10
Code or Value Value Description Count Cumulative Skip to Item
1 to 10 Range of Values 6939 6939
. Missing 556 7495

ENXTR1G - Trial 1 result status

Variable Name:
ENXTR1G
SAS Label:
Trial 1 result status
English Text:
Trial 1: Status of Exhalation Attempt
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Acceptable measurement 5999 5999
2 Could Not Obtain 297 6296
3 < 5 ppb 643 6939
4 > 300 ppb 0 6939
. Missing 556 7495

ENXTR1Q - Trial 1 FENO Measurement (ppb)

Variable Name:
ENXTR1Q
SAS Label:
Trial 1 FENO Measurement (ppb)
English Text:
Trial 1 measurement of fractional concentration of orally exhaled nitric oxide (FENO) in parts per billion
Target:
Both males and females 6 YEARS - 79 YEARS
Hard Edits:
5 to 300
Code or Value Value Description Count Cumulative Skip to Item
5 to 177 Range of Values 5999 5999
. Missing 1496 7495

ENXTR2G - Trial 2 result status

Variable Name:
ENXTR2G
SAS Label:
Trial 2 result status
English Text:
Trial 2: Status of Exhalation Attempt
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Acceptable measurement 6131 6131
2 Could Not Obtain 56 6187
3 < 5 ppb 453 6640
4 > 300 ppb 0 6640
. Missing 855 7495

ENXTR2Q - Trial 2 FENO Measurement (ppb)

Variable Name:
ENXTR2Q
SAS Label:
Trial 2 FENO Measurement (ppb)
English Text:
Trial 2 measurement of fractional concentration of orally exhaled nitric oxide (FENO) in parts per billion
Target:
Both males and females 6 YEARS - 79 YEARS
Hard Edits:
5 to 300
Code or Value Value Description Count Cumulative Skip to Item
5 to 205 Range of Values 6131 6131
. Missing 1364 7495

ENXTR3G - Trial 3 result status

Variable Name:
ENXTR3G
SAS Label:
Trial 3 result status
English Text:
Trial 3: Status of Exhalation Attempt
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Acceptable measurement 1277 1277
2 Could Not Obtain 28 1305
3 < 5 ppb 128 1433
4 > 300 ppb 1 1434
. Missing 6061 7495

ENXTR3Q - Trial 3 FENO Measurement (ppb)

Variable Name:
ENXTR3Q
SAS Label:
Trial 3 FENO Measurement (ppb)
English Text:
Trial 3 measurement of fractional concentration of orally exhaled nitric oxide (FENO) in parts per billion
Target:
Both males and females 6 YEARS - 79 YEARS
Hard Edits:
5 to 300
Code or Value Value Description Count Cumulative Skip to Item
5 to 199 Range of Values 1277 1277
. Missing 6218 7495

ENXTR4G - Trial 4 result status

Variable Name:
ENXTR4G
SAS Label:
Trial 4 result status
English Text:
Trial 4: Status of Exhalation Attempt
Target:
Both males and females 6 YEARS - 79 YEARS
Code or Value Value Description Count Cumulative Skip to Item
1 Acceptable measurement 127 127
2 Could Not Obtain 5 132
3 < 5 ppb 3 135
4 > 300 ppb 0 135
. Missing 7360 7495

ENXTR4Q - Trial 4 FENO Measurement (ppb)

Variable Name:
ENXTR4Q
SAS Label:
Trial 4 FENO Measurement (ppb)
English Text:
Trial 4 measurement of fractional concentration of orally exhaled nitric oxide (FENO) in parts per billion
Target:
Both males and females 6 YEARS - 79 YEARS
Hard Edits:
5 to 300
Code or Value Value Description Count Cumulative Skip to Item
5 to 192 Range of Values 127 127
. Missing 7368 7495

ENXMEAN - Mean, 2 reproducible FENO measures (ppb)

Variable Name:
ENXMEAN
SAS Label:
Mean, 2 reproducible FENO measures (ppb)
English Text:
Mean of two reproducible FENO measurements, in parts per billion
Target:
Both males and females 6 YEARS - 79 YEARS
Hard Edits:
3.5 to 301
Code or Value Value Description Count Cumulative Skip to Item
3.5 to 197 Range of Values 6525 6525
. Missing 970 7495