Spirometry is a physiological test used to establish baseline lung function by measuring how an individual inhales or exhales volumes of air as a function of time. Spirometry is important as a screening test of general respiratory health.

Spirometry (section: physical state) is measured in Lifelines participants aged 8 years and older during:

• 1A Visit 1 (in 121.000 particpants, including ~10.000 children)
• 2A Visit 1 (in ~32.000 adult participants that also underwent the test at baseline)
• 3A Visit 1

Spirometry was performed following ATS guidelines using a Welch Allyn Version 1.6.0.489, PC-based SpiroPerfect with CardioPerfect Workstation software. The Welch Allyn SpiroPerfect device (spiroperfect_manual.pdf) consists of a pressure tubing (6.6 ft/2.0m), nose clip, disposable flow transducer and calibration syringe.

• Calibrate the device
• Inform the participant about the aim and procedure of the measurement
• Mention that the measurement will be repeated several times in order to obtain a reliable measurement
• Check contraindications
• Check if participants has constrictions given by a physician/specialist
• Give instructions to participant:
  • Turn the chair
  • Sit straight with legs next to each other
  • Do not lean forward while exhaling in the tube
  • Place the nose clip with patch
  • Take the tube in your mouth, hold with your teeth and place the lips around the tube
  • Exhale 10 times with maximum effort. After each test you receive new instructions about the blowing technique
• In- and exhale technique:
  • Inhale as deep as possible (quick is not necessary)
  • Exhale as hard and powerful as possible
  • Continue expiratory effort to a maximum, until unable to continue
  • On my sign (PA) you inhale as fast en deep as possible
• Initialize before each test, whereby the tube observes no airflow. It is important that the participants do not move the tube.

Calibration of the device was performed at login and again after 4 hours, as follows:

• Humidity, barometric pressure and termperature are registered
• A pressure tube is placed on the spirometer, and the calibration syringe is connected
• The calibration syringe is pulled out before starting with calibration > click OK
• After 3 seconds, the syringe is pushed in and pulled out once, following the pace of the blue bar
• Result of the calibration are checked,
  • deviation is less than 3% of 3 liter? OK
  • deviation is more than 3% of 3 liter? Try again

Spirometry systems should be evaluated using a computer-driven mechanical syringe or its equivalent, in order to test the range of exhalations that are likely to be encountered in the test population. Computer-controlled mechanical syringes (i.e. pump systems) used for validation should be accurate within ±50 mL, which is 0.5% of their full range up to 10L.

Spirometry should not be performed on participants who need to avoid increased pressure situations, for example due to the following:

• Recent eye surgery (< 6 wks)
• Recent thorax-/abdominal surgery (< 6wks)
• Recent operation on umbilical hernia/ incisional hernia (< 6 wks)
• Presence of umbilical hernia/incisional hernia and hernia
• Pneumothorax (< 6 wks)
• Spontaneous pneumothorax (more than twice)
• Rib fracture
• Recent lung embolism (2 - 6 wks)
• Recent infarct ( 2 - 6 wks)
• Recent heart catheterisation (< 2 wks)
• Aneurism
• Avoidance of (heavy) exertion as per instructions from doctor/ specialist
• Tuberculosis
• Recent airway infection (<3 wks)

Important aspects of spirometry are:

• FVC (Forced vital capacity): the determination of the vital capacity from a maximally forced expiratory effort
• FEV1 (Forced expiratory volume): a generic term indicating the volume of air exhaled under forced conditions in the first t seconds of an FVC manoeuvre from a position of full inspiration
• PEF (Peak expiratory flow): The highest forced expiratory flow measured with a peak flow meter
• FEF (Forced expiratory flow): related to some portion of the FVC curve; modifiers refer to amount of FVC already exhaled
• FIVC (Forced inspiratory vital capacity). The maximum volume of air (in liters) that can be inspired during forced inspiration starting from full expiration.

• de Lichtenfels, AJFCA et al. (2018) Long-term air pollution exposure, genome-wide DNA methylation and lung function in the lifelines cohort study. Environmental Health Perspectives 126(2): 027004
• de Jong, K. et al. (2017) Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure. Respiratory Research 18(1): 142
• Soler Artigas, M et al. (2011) Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nature Genetics 43(11): 1082-1090
• Hobbs, BD et al. (2017) Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. Nature genetics 49(3): 426-432
• de Jong, K et al. (2013) GST-omega genes interact with environmental tobacco smoke on adult level of lung function. Respiratory Research 14(1): 83
• Hancock, DB et al. (2012) Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function. PLOS Genetics 8(12): e1003098
• van der Plaat, DA et al. (2017) Genome-wide association study on the FEV1/FVC ratio in never-smokers identifies HHIP and FAM13A. Journal of Allergy and Clinical Immunology 139(2): 533-540
• de Jong, K et al. (2014) NOS1: A Susceptibility Gene for Reduced Level of FEV1 in the Setting of Pesticide Exposure. American Journal of Respiratory and Critical Care Medicine 190(10): 1188-1190
• de Jong. K et al. (2015) Genome-wide interaction study of gene-by-occupational exposure and effects on FEV1 levels. Journal of Allergy and Clinical Immunology 136(6) 1664-1672