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Exhaled and nasal nitric oxide measurement 

Exhaled and nasal nitric oxide measurement
Exhaled and nasal nitric oxide measurement

Jeremy Hull

, Julian Forton

, and Anne Thomson

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Exhaled nitric oxide

  • The measurement of NO concentration in exhaled air is a reproducible, non-invasive method of assessing airway inflammation.

  • Levels <18 ppb are defined as normal. In practice, baseline levels vary between individuals, and a change in level is more informative than a single measurement.

  • NO levels are increased in the nasal, sinus, and oral cavities. There is also the possibility of ambient NO contamination. True lower airway levels are defined as the plateau level achieved through mid expiration.

  • To minimize contamination from the nasal cavity and sinuses, exhalation is carried out against a fixed pressure, causing the soft palate to close off the nasopharynx. Contamination from the atmosphere is minimized by inspiring air with a very low NO concentration (<5 ppb). This is achieved in some devices by inhaling through the device.

  • The single breath online measurement method is the preferred method in all children who can cooperate. The child is required to inhale to near total lung capacity (TLC) and then exhale at a constant flow rate against a resistance for 6–10 s. Audiovisual aids can assist in these manoeuvres, but they can still be difficult for some children. Wearing a nose clip is not recommended, since it may result in nasal contamination.

  • An offline method can also be used, again with the child exhaling at a constant flow rate. The child exhales into an inert balloon. NO concentrations can be stable for several hours. With the newer handheld portable NO devices, offline methods have largely been superseded by constant flow methods.

  • Whichever device is used, the analyser will measure the FENO in parts per billion.

  • Exhaled NO levels are elevated in patients with asthma, suppressed in patients with PCD, and relatively low in children with CF. Exhaled NO levels for other conditions are shown in Table 70.1.

  • In the short term, exhaled NO levels are reduced by exercise, spirometry, and sputum induction manoeuvres. These should therefore be avoided before NO measurement.

  • Measurements of FENO can be made during tidal breathing in very young children. The values obtained are not equivalent to single breath measurements, and age-related normal values have yet to be established. The use of FENO by this method is currently only as a research tool.

Table 70.1 Effect of various diseases on FENO





↓; ↑ with respiratory exacerbations


Pulmonary hypertension

↓ or ↔


↔ or ↑

Viral infection

↔ or ↑

Allergic rhinitis

↔ or ↑


Lung rejection post-transplant


Chronic cough






* ↑, increased; ↓, decreased; ↔, normal.

Nasal nitric oxide

  • The levels of NO in the nasal cavity and paranasal sinuses are several fold higher than those found in the lower airways.

  • The exact source of the gas is not known.

  • For most conditions, such as CF or allergic rhinitis, the significance of the level of nasal NO is not clearly understood.

  • In children with PCD, nasal NO levels are consistently lower than in control subjects, and the measurement of nasal NO can assist in the diagnosis of this condition (see Exhaled and nasal nitric oxide measurement Chapter 34).

  • Unlike measurements of exhaled NO, there are no commercially available simple-to-use, portable devices for measuring nasal NO. Measurement of nasal NO is only available in specialist centres.

  • The preferred method of measuring nasal NO requires air to be aspirated from one nostril at a constant rate (0.25–3 L/min), whilst it is entrained through the other nostril. To prevent contamination from ambient air, the nostrils are plugged with olives, through which the sampling catheters are passed. To prevent contamination from the lower airways, the child must exhale against a fixed resistance of at least 10 cmH2O to close the soft palate. NO levels take 15–30 s to plateau.

  • The requirements of the test mean that it can only be used on cooperative older children (generally >5 years of age).

  • Normal values range between 150 and 1000 ppb. Values in PCD are usually <100 ppb. Low values are also seen in children with blocked noses, sinus disease, or CF. There is no published cut-off level which excludes a diagnosis of PCD.

Further information

American Thoracic Society; European Respiratory Society (2005). ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med 171, 912–30.Find this resource: