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Keywords:

  • clinical applications;
  • lung function test;
  • spirometry

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

The development and clinical application of lung function tests have a long history, and the various components of lung function tests provide very important tools for the clinical evaluation of respiratory health and disease. Spirometry, measurement of the diffusion factor, bronchial provocation tests and forced oscillation techniques have found diverse clinical applications in the diagnosis and monitoring of respiratory diseases, such as chronic obstructive pulmonary disease, interstitial lung diseases and asthma. However, there are some practical issues to be resolved, including the establishment of reference values for individual test parameters and the roles of these tests in preoperative risk assessment and pulmonary rehabilitation. Novel measurements, including negative expiratory pressure, the fraction of exhaled nitric oxide and analysis of exhaled breath condensate, may provide new insights into physiological abnormalities or airway inflammation in respiratory diseases, but their clinical applications need to be further evaluated. The clinical application of lung function tests continues to face challenges, which may be overcome by further improvement of conventional techniques for lung function testing and further specification of new testing techniques.


INTRODUCTION

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

Since Borelli first measured lung volumes in 1679, the development of lung function tests has evolved tremendously. Further exploration of the principles of lung function tests, improvements in instrumentation and methodology, and the promotion of clinical applications have continued since the 1970s. Lung function tests have become an indispensable tool for the clinical evaluation of respiratory health and disease. In recent years, the establishment of guidelines for performing lung function tests has given these tests even wider clinical application in different clinical scenarios. However, there are some theoretical and practical issues that need to be resolved, and these issues have remained controversial over recent decades. This review is not meant to be exhaustive but aims to provide an update on recent understanding and developments in different aspects of lung function testing and related issues that are relevant to clinical practice.

SPIROMETRY

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

Spirometry is a relatively simple, non-invasive method for measuring the flow and volume of air from full lung inflation as a function of time using forced manoeuvres.1 It is widely accepted as a clinical tool for diagnosing obstructive, restrictive or mixed ventilatory defects.2 Spirometry plays an essential role in the diagnosis and management of respiratory diseases, especially asthma and chronic obstructive pulmonary disease (COPD).3,4 However, no gold standard reference tests exist to allow accurate determination of the sensitivity and specificity of spirometry for establishing the presence of airflow limitation.

A ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) of <0.7 has been taken to indicate airflow limitation. The use of a fixed ratio may offer an easy method for defining airflow limitation, and most recent guidelines, including the Global Initiative for Chronic Obstructive Lung Disease and Interpretative Strategies for Lung Function Tests, continue to define airflow limitation in terms of a fixed FEV1/FVC ratio.2,3 However, this definition of airflow limitation is not perfect and has been criticized for leading to underdiagnosis in younger subjects and overdiagnosis in elderly subjects. Thus, non-smoking elderly subjects were found to have an FEV1/FVC ratio of <0.7 but had no respiratory symptoms. This would lead to false-negative results and false-positive results, respectively, in those specific age strata, that is, failure to identify airflow limitation in young subjects with clinical symptoms, but the labelling of asymptomatic non-smoking elderly subjects as having ‘COPD’.5 The current American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines suggest the use of statistically derived lower limits of normal values for FEV1/FVC rather than a fixed ratio.2 The lower limits of normal is usually based on confidence intervals around the lowest fifth percentile of a reference population and is considered a potentially better way of identifying airflow limitation in elderly subjects. The use of lower limits of normal would, however, imply the availability of reference values for a specific population. Consensus has not been reached on whether a fixed ratio or lower limits of normal is more suitable for defining airflow limitation.

The FVC, on the other hand, is highly dependent on effort and cooperation from the subject. In order to complete the FVC manoeuvre and meet the acceptability and reproducibility criteria, subjects must expel air forcefully and completely in at least three attempts. This is particularly demanding and difficult for elderly subjects and those with severe airflow limitation. In patients with severe respiratory disease, the manoeuvre may take as long as 20 s and may also entail a risk of syncope.1 In recent years, the forced expiratory volume in 6 s has been proposed as a complementary or even substitute measurement for FVC in specific clinical situations.6 Measurement of forced expiratory volume in 6 s may require less effort from the patient, and forced expiratory volume in 6 s appeared to be more reproducible than FVC and provided a more precise definition of end-of-test.7 A recent meta-analysis showed that FEV1/forced expiratory volume in 6 s was a sensitive and specific parameter for the diagnosis of airflow limitation.8

Spirometry is not recommended for screening for airflow limitation in asymptomatic individuals. As suggested in the latest joint American College of Physicians/American College of Chest Physicians/ATS/ERS clinical guidelines, spirometry should be performed to diagnose airflow limitation in patients with respiratory symptoms; however, there was insufficient evidence to support the use of spirometry to screen for airflow limitation in individuals without respiratory symptoms, including smokers with defined levels of tobacco smoking.9 Moreover, the use of inhaled therapies in asymptomatic individuals with or without spirometric evidence of airflow limitation is not recommended.9,10 Current evidence also does not suggest any significant benefit of regular spirometry after initiation of therapy for monitoring disease status or guiding therapy in symptomatic patients.9,10

During tidal breathing, patients with severe COPD and other lung diseases often exhale along the same flow-volume curve, and the term ‘tidal expiratory flow limitation’ was introduced to indicate that maximal expiratory flow is achieved at rest or during exercise. The important role of tidal expiratory flow limitation in chronic dyspnoea and exercise impairment in a wide range of clinical circumstances was highlighted by available physiological techniques, particularly the negative expiratory pressure technique, which should probably be regarded as the new standard for detecting tidal expiratory flow limitation.11 This method does not require FVC manoeuvres, cooperation of the subject or the use of a body plethysmograph, and can be used for spontaneously breathing subjects independent of body posture. The negative expiratory pressure technique may provide new insights into the physiology and pathophysiology of specific respiratory diseases such as COPD.12

Restrictive ventilatory defects may also be detected by spirometry. A low FVC together with a normal or high FEV1/FVC ratio may suggest, but is not diagnostic for, restrictive abnormality.2 A decreased vital capacity has been regarded as the main indication of a restrictive pattern. The measurement of vital capacity is simple, but a reduction in vital capacity can either reflect true restriction, or airflow limitation that leads to excessive air trapping, or early termination of the expiratory effort. Measurement of total lung capacity, which may be an indicator of the real lung volume, independent of flow limitation, seems to be essential. Although equivalent total lung capacity values may be derived using either the helium dilution or whole-body plethysmography methods,13 the presence of air trapping in elderly subjects or heterogeneous alveolar gas distribution in COPD may lead to significant differences between the two methods.14

Diagnosis of respiratory disease by spirometry requires comparison of the results with reference values from the same population, corrected for age, height, gender and ethnicity. It is unrealistic to expect each lung function laboratory to establish its own set of reference values. However, it has been proposed that reference equations that are derived from the same population with ATS/ERS compliant instruments and testing procedures should be used.15 It is also preferable that updated reference equations are available for prediction of spirometry parameters in a specific population.16

Numerous studies have reported on the preoperative risk assessment of patients undergoing lung resection, and spirometry is indicated in such clinical scenarios in order to estimate postoperative FEV1 and assess the functional outcomes of pulmonary resection.17,18 In patients undergoing other high-risk procedures such as abdominal, aortic or non-resective thoracic surgery, preoperative pulmonary function tests have a limited role. Some investigators have suggested that clinicians could identify patients who are at high risk using clinical criteria and that the results of spirometry are unlikely to modify the clinical risk estimate.19

Pulmonary rehabilitation has been advocated in recent decades so as to provide comprehensive care and improve the functional status of patients with chronic respiratory diseases. A meta-analysis examined the results from 31 randomized controlled trials and concluded that in patients with COPD, pulmonary rehabilitation significantly improved symptoms and overall quality of life but that the efficacy of restoration of pulmonary function had not been assessed.20 In another study, the lung function of 119 patients did not show significant improvement despite the fact that they were randomized to receive rehabilitation.21 It should be emphasized, however, that improvement in lung function is not the only goal of pulmonary rehabilitation, and the contribution of a comprehensive pulmonary rehabilitation program to the overall physical and psychological health of patients is beyond doubt.

DIFFUSING CAPACITY

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

According to the model of Roughton and Forster,22 the process of carbon monoxide uptake can be simplified into two transfer or conductance properties: membrane conduction (DM), which represents the passage of carbon monoxide through the alveolocapillary membrane, and blood conduction (θVc), which reflects the reaction rate (θ) of carboxyhaemoglobin and the volume of alveolar-capillary blood. DM and volume of alveolar-capillary blood can be estimated from the diffusing capacity for carbon monoxide (DLCO) measured at two levels of inspired oxygen fraction: normal (21% O2) and high (50% O2), as shown in the following equation:

  • image(1)

Previous studies have determined the clinical values of DM and volume of alveolar-capillary blood in conditions such as COPD and sarcoidosis.23,24 Although separate measurements of DM and volume of alveolar-capillary blood may help in the assessment of abnormal pulmonary gas exchange and facilitate early intervention, these tests have not become standard tools in the pulmonary function laboratory. In the aforementioned Equation 1, θ is an estimate, and the value of DM is determined over two separate periods at different inspired oxygen fraction values during which several factors may influence the measurement.25

Different techniques, including steady-state, intrabreath and rebreathing techniques, may be used to estimate DLCO.26–28 The single-breath technique is the method of choice, as it does not require arterial blood sampling or meticulous timing of alveolar samples. The measurement is usually performed according to the joint ATS/ERS statement.29

Reference values for DLCO are determined in relation to gender, age, height, weight and haemoglobin concentration.29 The reference values of Miller and associates30 were developed in Michigan, and another set of reference equations for non-smoking Chinese subjects was developed in Hong Kong.31

A decrease in the gas exchange area of the lungs or the volume of blood in the pulmonary capillaries, an increase in the alveolocapillary membrane thickness, and ventilation-perfusion mismatching will lead to a reduction in DLCO.32 Low DLCO has been generally described in interstitial lung diseases and sarcoidosis.24 Small airway disease, chronic airway inflammation and involvement of the lung parenchyma may also manifest as a reduction in DLCO.33 Chronic pulmonary embolism, primary pulmonary hypertension (PPH) and other pulmonary vascular diseases may also result in a decline in DLCO.34 There are known associations between reduced DLCO and clinical conditions such as mixed connective tissue disease,35 gastro-oesophageal reflux,36 diabetes mellitus37 and liver cirrhosis.38 It is therefore crucial for clinicians to have a clear understanding of how lung function, and in particular DLCO, is affected by these extrapulmonary diseases. The decrease in DLCO can be classified into different degrees of severity, with a % predicted DLCO of 60% to the lower limits of normal indicating mild impairment, 40–60% moderate impairment and <40% severe impairment.2

The causes of a high DLCO are less well defined. Alveolar haemorrhage,39 asthma40 and obesity41 all lead to an increase in DLCO. However, some studies have shown conflicting results. Saydain et al.42 confirmed that an increased DLCO was commonly associated with a clinical diagnosis of obesity and asthma. Other unusual causes of a high DLCO are pulmonary haemorrhage, polycythaemia and left-to-right shunt.

Krogh43 once described DLCO as the product of two separate measurements—the rate constant for removal of carbon monoxide from alveolar gas, which is referred to as the transfer coefficient (Kco or DLCO/VA), and the alveolar volume (VA). This simple concept is the key to its clinical application, and it is logical to examine both DLCO and its components simultaneously.44 A low DLCO will usually be associated with a low Kco or a low VA, or a combination of these two factors. It is also possible for the Kco to be high, but it is unusual for VA to exceed its predicted normal value.45 In emphysema and diffuse alveolar-capillary damage associated with connective tissue or autoimmune disease, thickening or inflammatory changes in the extravascular tissues result in a low Kco, while obstructive or restrictive mechanisms reduce VA, and all these factors contribute to a decline in DLCO. In addition, loss or destruction of the pulmonary capillary bed in pulmonary thromboembolism and congestive heart failure also result in a decrease in Kco and DLCO, although VA is normal in these diseases. In other clinical scenarios, such as pneumonectomy or chest-wall deformity, in which pulmonary blood flow is diverted from the diseased region to a normal region, increased blood flow per unit volume leads to a high Kco but may be associated with a high, normal or low DLCO depending on whether the total effective VA is normal or reduced.44 As pointed out by Hughes and Pride, in disease, different combinations of Kco and VA may occur for a given value of DLCO, with each pattern providing different pathophysiological information.44,45 Therefore, inspection of the two components of DLCO is essential if reasonable interpretations of this test are to be made. Figure 1 lists the possible causes of a low DLCO associated with some common pulmonary diseases.

image

Figure 1. Low diffusing capacity for carbon monoxide (DLCO) and its components in some common pulmonary diseases. Kco, transfer coefficient; VA, alveolar volume.

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DLCO and Kco continue to be important measurements for clinical assessment of pulmonary gas exchange in both pulmonary and extrapulmonary diseases. The ATS and ERS recommendations for normal predictive equations will facilitate the development of standard applications for DLCO measurements in the future.

BRONCHIAL PROVOCATION TEST

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

Bronchial provocation tests (BPT) or bronchial challenge tests are used to assess bronchial hyperresponsiveness (BHR) or airway hyperresponsiveness through various means of stimulating the airway. The provocation agents can be broadly classified into two categories: direct and indirect, with the latter including adenosine monophosphate, exercise, hypertonic saline, eucapnic hyperventilation and mannitol. Direct stimuli, such as histamine and methacholine, act on airway smooth muscle receptors, and indirect stimuli act through one or more intermediate pathways, including release of mast cell mediators, and local and central neurological reflexes.46

The arbitrary cut-off points for direct BPT have been defined so as to provide maximal sensitivity but not maximal specificity,47 and a positive test result is consistent with, but not diagnostic for, asthma. On the other hand, indirect BPT is superior for confirming a diagnosis of asthma but are insensitive, particularly in patients with mild or well-controlled asthma.48,49 Van Schoor et al. hypothesized that indirect airway responsiveness may correlate better with the clinical features of asthma, including severity, activity, underlying inflammation and response to anti-inflammatory treatment.50 Technical factors, including generation of the aerosol, method of inhalation, measurement and calculation of response, must be strictly controlled according to a standard procedure. Factors that may influence airway responsiveness are medications such as β2-agonists, theophylline, tiotropium and corticosteroids, which may decrease airway responsiveness. Other factors including recent exposure to allergens, recent respiratory tract infections and smoking will increase airway responsiveness.47 The overall risk of serious adverse events during BPT is small;51 however, abrupt falls in FEV1 may occur so impaired baseline pulmonary function is a relative contraindication. The provocative concentration that results in a 20% fall in FEV1 is selected as the endpoint of the test.

BHR may occur in a wide variety of diseases, including asthma, COPD, allergic rhinitis, cystic fibrosis and cardiac disease.52–54 There are significant associations between BHR and respiratory symptoms, including cough, shortness of breath and wheeze in COPD patients.55 However, a significant proportion of individuals with BHR do not have respiratory symptoms and may be considered to have asymptomatic or ‘silent’ BHR, or else, this could indicate COPD with an asthmatic component.56

BPT is a valuable tool for assessing the severity and progression of both asthma and COPD.57 In asthmatic patients, the degree of BHR is associated with the subsequent decline in pulmonary function.58 Follow-up studies on patients with COPD have shown that BHR is correlated with the annual rate of decline in FEV1,59 and abnormal BHR has been identified as an independent risk factor for increased mortality.60

Current guidelines on the step-wise management strategy for asthma and COPD state that the dosage and adjustment of inhaled corticosteroid (ICS) therapy should be guided by symptoms and lung function.3,4 However, many patients whose disease is considered to be clinically controlled may still have BHR and airway inflammation.61 Many studies have shown that when BHR is used to guide treatment with ICS, there is a further improvement in symptoms, lung function and airway biopsy findings, as compared with conventional assessment.62 It may be speculated that the application of such a management strategy to the long-term treatment of airway diseases may eventually result in the reduction of ICS doses.

IMPULSE OSCILLOMETRY

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

In the 1950s, the forced oscillation technique was introduced to evaluate airway resistance and reactance. In 1993, impulse oscillometry (IOS) was introduced by Jaeger (Hoechberg, Germany), as a user-friendly commercial apparatus for measurements of respiratory system resistance (R) and reactance (X) at a series of frequencies ranging from 0.1 to 150 Hz. This approach involves the superposition of the rectangular pressure impulse from a loudspeaker on spontaneous breathing, and the resulting pressure and flow changes are analysed to calculate respiratory impedance (Z).63

The basic output signals are affected mainly by the calibre of the central airways, and the elasticity and inertia of the airways, lung tissue and thorax.63 As high-frequency oscillations (>15–20 Hz) are not transmitted to the peripheral airways, these frequencies only reflect effects on the large airways; low-frequency oscillations (5–15 Hz) may be transmitted to the peripheral airways and therefore reflect both large airway and small airway function.63

IOS has several advantages over spirometry and body plethysmography for the evaluation of airway disorders. Conventional spirometry performed during forced breathing manoeuvres may itself influence bronchial smooth muscle tone.64 Body plethysmography is a sensitive method for measuring airway resistance (Raw), but it is also complex and time-consuming, requiring sophisticated instruction and good comprehension by the patient. In contrast, IOS is a simple technique for measuring respiratory resistance and is effort-independent. Furthermore, IOS can be used to give measurements of resistance across a variety of frequencies to differentiate functional indices from either the peripheral or central airways.63 IOS has found increasing application in clinical practice.65

IOS requires minimal cooperation from the subject and appears to be the only technique allowing measurements of respiratory mechanics with equal ease in children, adolescents and adults, as well as the elderly, which makes it possible to compare pulmonary function among different populations. IOS has been used to assess the mechanical properties of the airways in respiratory diseases such as asthma,66 COPD,67 cystic fibrosis68 and obstructive sleep apnoea syndrome.69 IOS has also been found to be more effective for identifying asthma, and assessing airway reactivity and bronchodilator responsiveness in specific clinical conditions.67,69 In patients with COPD, expiratory flow limitation during tidal breathing is considered to be a major determinant of dynamic hyperinflation, and as IOS can be used to distinguish the pathological mechanisms of airflow limitation, it is considered the preferred technique for measuring bronchodilation in clinical trials for COPD.67 In addition, IOS indices have been shown to be useful for evaluating upper airway patency in patients with obstructive sleep apnoea syndrome. Airway resistance measured by IOS was found to be closely associated with the apnoea/hypopnoea index.69

Although many studies have indicated its potential usefulness, IOS methodology has not been scrupulously evaluated according to published recommendations, including the input signals and frequencies, data processing, and acceptance, and validation of measurements.65 Further studies should be undertaken to assure the quality of measurements performed by IOS. In addition, one of the limitations of IOS in the clinical setting is the lack of reference values. There is a need to establish reference equations and to determine clear cut-off points in order to differentiate respiratory disease from normal lung function.

The previously mentioned conventional tests have been widely used in the diagnosis and treatment of many respiratory diseases and other conditions. It should be emphasized that cough and dyspnoea are the most common respiratory symptoms, and several guidelines from the American College of Chest Physicians,70 ERS71 and other countries have summarized evidence-based knowledge of the causes, optimal testing sequences and treatment of chronic cough. The role of lung function tests, such as spirometry, BPT and induced sputum analysis, in the diagnosis of chronic cough has been assessed. In addition, many respiratory diseases may cause dyspnoea, and lung function tests could offer methods for the differential diagnosis and effective assessment of impaired lung function. The suggested testing sequences for the differential diagnosis of dyspnoea based on lung function tests are shown in Figure 2.

image

Figure 2. Interpretative strategy for lung function tests for the clinical evaluation of subjects with dyspnoea. COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; ILD, interstitial lung disease; VC, vital capacity.

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NEWER MEASUREMENTS

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

The presence of endogenous nitric oxide (NO) in the exhaled breath of animals and humans was first described in 1991.72 Since then, there has been great interest in measuring the fraction of exhaled NO (FeNO) in subjects with asthma and other pulmonary diseases.73,74 Exhaled NO is mainly derived from the lower respiratory tract and is produced by the reaction catalysed by NO synthase. The inducible form of this enzyme is expressed in a variety of cells (e.g. epithelial and inflammatory cells) and is induced by pro-inflammatory mediators.75 There has been sustained interest in the measurement and application of FeNO as a potentially useful non-invasive index of airway inflammation.74

Airway inflammation is the basic pathophysiological mechanism; therefore, relevant assessment of airway inflammation may have significant implications for the diagnosis and management of different inflammatory airway disorders. Direct sampling of airway cells and mediators can be achieved using techniques such as bronchoscopy with biopsy and lavage. However, these procedures are invasive. Routine non-invasive tests, such as eosinophil counts in peripheral blood and analysis of induced sputum, may also be used. These highly reproducible measurements can be used to identify the presence, type and severity of airway inflammation, but they suffer from a lack of sensitivity and specificity, and the procedures are time-consuming. Recently, FeNO has been used as a biomarker for the assessment of airway inflammation.76 The advantage of FeNO is that the procedure is completely non-invasive, simple, safe and standardized, and that measurements can be repeated at different stages of the disease.

The ATS and ERS have issued a statement on recommended standardized methods for measuring FeNO.77 FeNO measurements can be affected by many factors, and flow rate is very important because FeNO levels are flow dependent. Subjects are required to maintain a constant expiratory flow (50 mL/s) and a positive expiratory pressure in order to accentuate the NO signal.78

Given the importance of FeNO as an indicator of airway inflammation, it is essential to define normal values in a healthy population. Although some studies have investigated reference values that take into consideration the common factors (e.g. age, height, weight, gender and race79) affecting FeNO in both children80 and adults,81 FeNO is subject to constitutional heterogeneity and varies with disease states making it difficult to precisely distinguish, as well as to define cut-off values for, normal and abnormal measurements.82

FeNO has also been reported to be mildly increased in patients with COPD,83 cystic fibrosis,84 bronchiectasis85 and upper respiratory tract infections.86 FeNO is raised in both stable and acute asthma, which is also characterized by airway inflammation.74,87 An elevated FeNO is not specific for and cannot be regarded as diagnostic for asthma. Many studies have shown that FeNO has a significantly higher negative predictive value for the diagnosis of asthma, suggesting that it has a potential role as a screening tool for assessing airflow limitation in asthma.88 FeNO is not associated with the severity of asthma but provides complementary information to that provided by respiratory symptoms and pulmonary function assessments.89

Asthma is characterized by airway inflammation, and ICS is currently the most effective treatment at doses that should be the minimum required to control symptoms. Current guidelines recommend that ICS treatment should be adjusted according to frequency of symptoms and respiratory function.4 However, neither of these two variables correlates closely with underlying airway inflammation. The measurement of airway inflammation as an endpoint to guide anti-inflammatory treatment appears to be logical. Cumulative evidence supports the use of FeNO as a useful clinical tool for the evaluation and on-going management of asthmatic patients.74,90 FeNO is higher in untreated patients than in patients with well-controlled asthma, and FeNO levels decrease after treatment with ICS.91 In asthmatic patients who were treated with ICS, FeNO correlated with markers of disease control, including asthma symptoms, disease score and reversibility of airflow limitation.92

FeNO is beginning to show promise for monitoring airway inflammation and for guiding optimal anti-inflammatory therapy in patients with chronic inflammatory airway diseases, and its clinical utility has been further confirmed and enhanced in the latest guidelines for interpretation of FeNO measurements.82 Compared with conventional tests such as BPT or the reversibility of FEV1, measurement of FeNO may offer more advantages for patient care, including but not limited to (i) detection of eosinophilic airway inflammation, (ii) prediction of clinical response to ICS therapy, (iii) monitoring of airway inflammation to guide maintenance ICS therapy, and (iv) detection of suboptimal compliance with ICS therapy.82 Prospective studies on measurement of FeNO in different clinical settings are warranted.

Other non-invasive and simple methods, including analysis of exhaled breath condensate and induced sputum, are alternative tools for the investigation of physiological and pathological mechanisms in the airways.93,94 However, non-standardized measurement procedures, variability of sample analysis and the lack of reference values all limit the clinical validity and utility of these techniques. Only by focusing on the previously mentioned problems in future studies can the application of biomarkers in pulmonary diseases be advanced from experimental research to the clinical arena.95

CONCLUSION

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES

The introduction and development of techniques for lung function testing have a long history, and up to the present, lung function testing has been an essential tool for the clinical evaluation of respiratory health and disease. It is only when used in close association with clinical practice that these techniques and methodology can be further improved and new parameters for lung function testing perfected.

REFERENCES

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. SPIROMETRY
  5. DIFFUSING CAPACITY
  6. BRONCHIAL PROVOCATION TEST
  7. IMPULSE OSCILLOMETRY
  8. NEWER MEASUREMENTS
  9. CONCLUSION
  10. REFERENCES