Lung function tests

Lung function tests are an important assessment tool in the diagnosis and management of

bronchiectasis. Lung function tests provide objective data about the type and degree of

respiratory impairment.

Patterns seen in bronchiectasis

Airflow obstruction is the most common ventilatory pattern seen in bronchiectasis, though

mixed obstructive/restrictive, restrictive or normal patterns can also be seen. The forced

vital capacity (FVC) may be reduced, often in conjunction with an elevated Residual Volume

(RV)/ Total Lung Capacity (TLC) ratio and normal to low TLC (1). Carbon monoxide transfer

factor (TLCO) – a measure of gas exchange is generally in the normal range – though it has

been shown to be reduced in more severe disease (1). Exhaled nasal nitric oxide levels have

been shown to be markedly reduced in those with cilial dysfunction (1).

How often should lung function be assessed?

The British Thoracic Society guideline for non-cystic fibrosis bronchiectasis (1) recommends

that adults and school age children should have spirometry measured at initial assessment.

They also recommend that adults attending specialist care have annual spirometry

performed, and those with immune deficiency or primary ciliary dyskinesia have spirometry

measured at least four times annually. Spirometry performed before and after antibiotic

use may be of value in assessing improvements objectively. Measures of static lung

volumes and gas exchange may be useful for identifying other causes of airflow limitation,

and assessment of bronchodilator response may be useful for identifying those with

reversible components to their airways disease. (1)

No recommendations for frequency for measuring nasal nitric oxide are made, though the

main purpose of the test is to identify those requiring further investigation for primary

ciliary dyskinesia.

Reactivity to inhaled hypertonic saline should be identified prior to considering commencing

patients on inhaled hypertonic saline to assist mucociliary clearance, though no clear

recommendation is given.

About the tests:

Aspects common to all tests:

Reference values

All results are compared to reference values (normal ranges) that have been derived from

large studies of lung function in people with good respiratory health (no evidence or history

of respiratory disease) and generally little to no smoking history. Lung function has been

shown to vary with gender, height, age, race and sometimes with weight in the normal

population. There are many reference sets for parameters of respiratory function and it is

important to keep in mind that the reference sets used may vary from laboratory to

laboratory. Large global reference datasets are now being developed and published (2) for

use worldwide.

Normal ranges

For test parameters where we are only interested in abnormally low results, we use a lower

limit of normal (LLN). For parameters where we are only interested in abnormal high results,

we use an upper limit of normal (ULN). For parameters of lung function where a result may

be abnormally high or low, we set both upper and lower limits of normal. The limits are

generally set so that 95% of the normal population sit within the normal range.

Interpretation

Interpretation of lung function is not discussed in detail on this website. For more detailed

explanations and cases, read (3), (4).

The measured values from a lung function test are compared to the reference values to

determine the pattern of impairment or normality. The measured values should also be

compared to previous results to look for changes (improvements or decline) over time.

Spirometry

Spirometry is one of the more common tests of lung function. Forced spirometry

manoeuvres measure how hard and fast a person can exhale from total lung capacity (TLC)

to residual volume (RV) and sometimes, how hard and fast they can breathe back in to TLC

again. The primary parameters of forced spirometry are the FEV1/FVC ratio, the FEV1

(forced expiratory volume in 1 second) and FVC.

To measure spirometry, the patient commences tidal breathing on a mouthpiece, with nose

peg in place to prevent leak. After a couple of tidal breaths, the patient is instructed to

breathe in maximally until full and then exhale as hard and as fast as they can until they are

very empty (Figure 1). The technique may differ slightly depending on the spirometer type

being used and may include a maximal breath in to TLC at the end of the manoeuvre.

Figure 1. Forced spirometry manoeuvre.

The vital capacity (VC), measured under relaxed conditions, is sometimes also measured. In

health, the VC and FVC should be very close to each other. In those with significant airflow

obstruction, there may be large differences between VC and FVC, with VC generally being

larger than FVC.

Spirometry tells us about whether the ventilatory pattern is within the normal range or

obstructed. Spirometry may also suggest potential restrictive or mixed

restrictive/obstructive patterns, but measurements of static lung volumes are required to

confirm these (Table 1).

Reversibility testing

Spirometry may be performed before and after the administration of a bronchodilator (most

often a beta-2 agonist such as salbutamol) to assess for reversibility of airflow obstruction. A

significant bronchodilator response is defined as an increase ≥ 12% AND ≥ 200mL in either

FEV1 or FVC (3) between pre-bronchodilator and post-bronchodilator tests. A significant

bronchodilator response in a well-performed test suggests that there is a component of

reversible obstruction that may respond to treatment.

Static lung volumes

Static lung volumes used in conjunction with spirometry help to better define ventilatory

patterns when parameters fall outside of the normal range. The parameter total lung

capacity (TLC) is used in 3 out of the 4 ventilatory pattern definitions (see Table 1). Total

lung capacity cannot be measured using spirometry. This is because there is always a small

amount of air left in the lung when we blow out until we are empty – the residual volume

(RV) – which is included in TLC (See figure 1).

Ventilatory Pattern Spirometry Static Lung Volumes

Obstruction (3) FEV1/(F)VC < LLNRestriction (3) FEV1/(F)VC > LLN AND TLC < LLNMixed Obstruction/Restriction (3) FEV1/(F)VC < LLN AND TLC < LLNNon Specific Ventilatory Pattern (5) FEV1/(F)VC > LLN,

FVC < LLN, FEV1 < LLNAND TLC > LLN

Table 1. Ventilatory patterns using spirometry and static lung volumes

For simple classification of ventilatory patterns, TLC is the primary parameter of static lung

volumes used. However, there are a number of other parameters that have been shown to

be useful in defining the degree of obstruction when it’s identified on spirometry. They

include: RV, functional residual capacity (FRC) and RV/TLC (see Table 2 and Figure 2).

SpirometryStatic Lung Volumes Possible Interpretation

Wor

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obst

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dise

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FEV1/(F)VC RV/TLC FRC TLC Obstruction with gas trapping Obstruction with hyperinflation (FRC) Obstruction with hyperinflation (TLC)

Table 2

Static lung volumes can be measured a number of ways. The most common methods are

body plethysmography and the washout/dilution methods. The basics of the methods are

described below. For detailed description of the methods, read (6)

Body Plethysmography

In body plethysmography, the subject sits in a box – a bit like a telephone booth (figure 3).

The box is sealed. After a short equilibration time, the subject is instructed by the operator

to undertake a series of breathing manoeuvres on a mouthpiece. During the breathing

manoeuvre, a shutter is closed in the mouthpiece and the subject continues to breathe

(small pants) against the closed shutter. While the shutter is closed, the pressure at the

mouth and the pressure in the box are measured. From this, the volume in the lung at can

be determined (usually FRC). When the shutter opens, the subject blows all the way out

until empty and then breathes in until full (figure 2) so that RV and TLC can be determined.

Figure 2. Volume trace for body plethysmographic measurement of static lung volumes.

Figure 3. Body Plethysomgraph.

Washout method

This technique washes out nitrogen (N2) from the lungs by breathing 100% O2. Basically, the

volume at which the washout began (usually FRC) can be calculated by measuring the initial

and final concentrations of N2 and the total volume exhaled. RV and TLC can then be

calculated using a separate SVC manoeuvre. For a more detailed explanation of the

methodology and calculations, read (6). In health, it may take up to 7 mins to wash out N2

from the lungs. In obstructive disease, it may take even longer.

Dilution method

The dilution method consists of breathing a special gas mixture (consisting of O2 and N2 and

an inert gas such as helium) of known volume and looking for inert gas concentration

equilibrium. The volume in the lungs at switch in to the circuit (usually FRC) can be

calculated using the initial and final inert gas concentrations and the system volume. Once

the FRC is known, RV and TLC can be calculated from a separate SVC manoeuvre. For a

more detailed explanation of the methodology and calculations, read (6). Like the washout

method, waiting for equilibrium can take a long time (10 min), particularly in those with

obstructive disease.

Limitations of test methods for measuring static lung volumes.

Each method for measuring static lung volumes has limitations. The plethysmographic

method may overestimate static lung volumes in significant obstruction and the washout

and dilution methods may underestimate lung volumes in significant obstruction.

Leak during the test will impact all methods of measuring static lung volumes, so if leak

occurs, the test should be terminated and recommenced.

Single breath carbon monoxide transfer factor (TLCO)

The primary purpose of the lungs is gas exchange; to get oxygen into the blood and remove

carbon dioxide from the blood. Spirometry and static lung volumes provide information

regarding ventilatory function and the single breath carbon monoxide transfer factor (TLCO),

provides information regarding gas exchange.

The test commences with the subject attaching to the mouthpiece with lips tightly sealed,

and normal breathing with nose pegs in place. After a few tidal breaths, the subject is asked

to breathe out to residual volume and then breathe in a special gas mixture rapidly to TLC.

Once at TLC, the subject breath holds for approximately 8 seconds before exhaling to RV

again. During the final exhalation, the first portion of the exhaled breath is discarded (as

dead space washout volume) and a sample is then collected for analysis (see figure 4). The

special gas mixture consists of nitrogen, oxygen, a very small amount of carbon monoxide

and an inert gas (such as helium, methane or neon).

Figure 4. Volume-time trace for the single breath carbon monoxide transfer test.

The initial and final concentrations of CO and the inert gas, along with the volume inspired

and breath hold time during the manoeuvre are used to calculate the carbon monoxide

transfer factor and the alveolar volume (VA), as well as other parameters of gas exchange.

For a more detailed explanation of methodology and calculations, read (7)

There are a number of factors that can effect TLCO measurement (Table 3). Some of these

factors can be accounted for by adhering strictly to test methodology and preparation.

Others can be accounted for by applying corrections to measured values. (7) Table 4 shows

some of the pathophysiological changes that result in either reductions or increases in TLCO.

Table 3. Factors affecting TLCO measurement

Decreased TLCO Increased TLCOAnaemia (low Hb, increased COHb) PolycythemiaHigh PIO2 (supplemental O2) Low PIO2 (test at altitude)

HypercapniaDecreased pulmonary capillary blood volume (valsalva manoeuvre)

Increased pulmonary capillary blood volume (mueller manoeuvre, exercise)Supine posture

Table 4. Pathophysiological causes of changes in TLCO

Pathophysiological causes of reduced TLCO Pathophysiological causes of increased TLCOReduction in alveolar membrane surface area e.g. emphysema, loss of lung units, incomplete alveolar expansion

Blood in alveolar spaces eg pulmonary haemorrhage

Alveolar membrane thickness increase e.g. pulmonary oedema, disorders of the interstitium

Changes in blood volume / distribution in the lungs e.g. asthma, obesity

Reduction in pulmonary capillary volume e.g. pulmonary hypertension, pulmonary embolus, microvascular destruction

Increased pulmonary capillary volume e.g. redistribution of blood flow following lung resection

In bronchiectasis, TLCO is usually within the normal range, though it has been noted to be

reduced in some people with end stage disease.

Exhaled nitric oxide (eNO)

Exhaled nitric oxide (eNO) can be measured as either alveolar or nasal nitric oxide (NO). The

nasal NO may be of value in identifying patients who may require further investigation of

their ciliary function. A low nasal NO level may indicate primary ciliary dyskinesia (8). The

technique for measuring exhaled nasal nitric oxide has become standardised in the past 10

years (9), though the standardised method for measuring nasal nitric oxide can be difficult

to perform in young children (<5 yr).

The technique for measuring nasal nitric oxide involves the sampling of the nasal passage

via one nostril with air entrainment via the other nostril. Nasal ‘olives’ with sampling tubes

are positioned in each nostril to ensure a leak free system. The velum should be closed to

eliminate alveolar NO and this can be achieved by taking the measurement while the

subject exhales against a resistance to generate a pressure of about 10 cmH2O. Ideally, air

entrained into nasal cavity should be NO free, hence air is entrained via an NO scrubber. The

measurement is minimally invasive, and each measurement takes approximately 10-20

seconds to make.

For a more detailed explanation of nasal nitric oxide measurement, read (9)

6% hypertonic saline assessment

Hypertonic saline (6%) may have some value in assisting mucociliary clearance in individuals

with bronchiectasis (10). Hypertonic saline has also been shown to cause

bronchoconstriction in those with currently active asthma and therefore it is important that

safety is assessed prior to commencement of hypertonic saline as part of therapy.

There is no standardise procedure for assessing safety of hypertonic saline, but assessment

generally consists of the following steps:

1. Review of recent clinical history – ideally subject should be clinically stable for 4 weeks

prior to assessment.

No admission to hospital within previous 4 weeks

No increase in respiratory medications or antibiotics in previous 4 weeks.

2. Baseline spirometry is measured

3. A short-acting bronchodilator is administered

4. Post bronchodilator spirometry is measured after waiting an appropriate time for

bronchodilator onset of action

5. Results are reviewed for the following:

Spirometry is compared to previous 6 months and should be within 10% of best

The response to inhaled bronchodilator should be non-significant (see Reversibility

testing)

FEV1 >1.00L

The referring doctor should be consulted if any of the conditions above are not met prior

to proceeding to determine safety to continue

6. Hypertonic saline is inhaled via nebuliser (preferably the one the subject will be using at

home) for 10 minutes, followed by a 20 minute rest

7. Spirometry is repeated. If FEV1 falls >15% from baseline FEV1 (pre-bronchodilator), this

indicates that airways are reactive to hypertonic saline and this therapy may pose a

safety risk in the individual.

Bibliography

1. Guideline for non-CF bronchiectasis. M C Pasteur, D Bilton, A T Hill. 2010, Thorax, Vol. 65, pp. i1-i58.

2. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J and Initiative, ERS Global Lung Function. 6, Dec 2012, European Respiratory Journal, Vol. 40, pp. 1324-43.

3. ATS/ERS task force: Standardisation of Lung Function tests. Interpretative strategies for lung function tests. R. Pellegrino, G. Viegi, V. Brusasco, R.O. Crapo, F. Burgos et al. 5, 2005, European Respiratory Journal, Vol. 26, pp. 948-68.

4. Borg BM, Thompson BR, O'Hehir RE. Interpreting Lung Function Tests: A Step-by-Step Guide. Chichester : Wiley Blackwell, 2014. 978-1-118-40551-2.

5. The nonspecific pulmonary function test: longitudinal follow-up and outcomes. Iyer VN, Schroeder DR, Parker KO, Hyatt RE, Scanlon PD. 2, Feb 2009, Chest, Vol. 135, pp. 419-24.

6. ATS/ERS Task Force: Standardisation of lung function testing. Standardisation of the measurement of lung volumes. J. Wanger, J.L. Clausen, A. Coates, O.F. Pedersen, V. Brusasco, F. Burgos et al. 2005, European Respiratory Journal, Vol. 26, pp. 511-522.

7. ATS/ERS TASK FORCE: STANDARDISATION OF LUNG FUNCTION TESTING. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. N. MacIntyre, R.O. Crapo, G. Viegi, D.C. Johnson, C.P.M. van der Grinten, V. Brusasco, F. Burgos et al. 2005, European Respiratory Journal, Vol. 26, pp. 720-735.

8. Diagnostic accuracy of nitric oxide measurements to detect primary ciliary dyskinesia. M Boon, I Meyts, M Proesmans, FL Vermeulen, M Jorissen, K De Boeck. 5, 2014, European Journal of Clinical Investigation, Vol. 44, pp. 477–485.

9. ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. 2005, American Journal of Respiratory and Critical Care Medicine, Vol. 171, pp. 912-930.

10. The long term effect of inhaled hypertonic saline 6% in non-cystic fibrosis bronchiectasis. CHH Nicolson, RG Stirling, BM Borg, BM Button, JW Wilson, AE Holland. 5, May 2012, Respiratory Medicine, Vol. 106, pp. 661-667.