Measuring fractional exhaled nitric oxide concentration in asthma: NIOX MINO, NIOX VERO and NObreath

3.1 Nitric oxide, which is produced in the lungs and is present in exhaled breath, has been implicated in the pathophysiology of lung diseases, including asthma. It has been shown to act as a vasodilator, bronchodilator, neurotransmitter and inflammatory mediator in the lungs and airways. Over the years, fractional exhaled nitric oxide (FeNO) has been proposed as a non‑invasive marker of airway inflammation in asthma. FeNO levels are raised in people with asthma and can be lowered by effective treatment with corticosteroids.

3.2 The purpose of this evaluation was to evaluate the clinical and cost effectiveness of measuring FeNO in the diagnosis and management of asthma.

3.3 Asthma is a chronic disorder of the airways, caused primarily by inflammatory processes and constriction of the smooth muscle in airway walls (bronchoconstriction). It is generally characterised by reversible airflow obstruction and increased responsiveness of the airways to various stimuli. Symptoms include recurrent episodes of wheezing, breathlessness, chest tightness and coughing. Typical asthma symptoms tend to be variable, intermittent and worse at night. Asthma is commonly triggered by viral respiratory infections, exercise, or external factors such as smoke, a change in weather conditions and allergens (for example, pollen, mould and house dust mites).

3.4 In people with asthma, cellular inflammation of the airways with eosinophils and neutrophils is considered to be a characteristic feature relevant to the pathogenesis of the disease. Eosinophilic asthma is a distinct phenotype of asthma associated with a rise in nitric oxide in exhaled breath. Eosinophilic asthma may respond to treatment with corticosteroids, while neutrophilic asthma generally does not.

3.5 Asthma usually develops in childhood but may start at any age. There is no cure for asthma, although people may have long periods of remission. Poorly controlled asthma can have a significant impact on the quality of life of the affected person and their family. Because there may be variation in an individual's perception of asthma symptoms, clinical measures such as lung function do not always correlate with quality-of-life scores. However, if asthma is well controlled, near-maximal scores on quality-of-life instruments can be achieved.

3.6 Asthma is diagnosed on the basis of symptoms and objective tests of lung function. Spirometry is used to assess lung function by measuring the volume of air that the patient is able to expel from the lungs after a maximal inspiration. Spirometry lung function measurements include peak expiratory flow rate (PEF), forced vital capacity (FVC; the total volume of air that a person can forcibly exhale in 1 breath), forced expiratory volume in the first second (FEV1) and percentage predicted FEV1 (calculated as a percentage of the predicted FEV1 for a person of the same height, sex and age without diagnosed asthma). Variability in PEF and FEV1, either spontaneously or in response to therapy, is a characteristic feature of asthma. The severity of asthma is judged according to symptoms and the amount of medication needed to control them, and is based on the British guideline on the management of asthma (2012) from the British Thoracic Society (BTS) and Scottish Intercollegiate Guidelines Network (SIGN).

3.7 Asthma is diagnosed clinically and there is no standardised definition of the condition. The presence of symptoms (wheezing, breathlessness, chest tightness and cough) and variable airflow obstruction is central to all definitions. More recently, descriptions of asthma have included airway hyper-responsiveness and airway inflammation. It is unclear how these features relate to each other, how they are best measured and how they contribute to the clinical manifestations of asthma.

3.8 The diagnosis of asthma in children is based on recognising a characteristic pattern of episodic symptoms in the absence of an alternative explanation. If asthma is suspected, an initial clinical assessment should be carried out to estimate the probability of asthma. According to the British guideline on the management of asthma (2012), a child can be classed into 1 of 3 groups based on initial clinical assessment. These groups are:

3.9 For children identified as having a low probability of asthma, a more detailed investigation and specialist referral should be considered. For children with a high probability of asthma, a trial of treatment should be started immediately. The response to treatment should be reassessed every 6 months. Those with a poor response to treatment should have more detailed investigations.

3.10 In children with an intermediate probability of asthma who can perform spirometry and have no evidence of airway obstruction, tests for atopic status, assessment of bronchodilator reversibility and, if possible, tests for bronchial hyper-responsiveness using methacholine, exercise or mannitol should be considered. In such cases, specialist referral should always be considered.

3.11 The diagnosis of asthma in adults is based on clinical history and includes the recognition of a characteristic pattern of symptoms and signs, and the absence of an alternative explanation for them. Spirometry is the preferred initial test to assess the presence and severity of airflow obstruction. Adults are also classified as having a high, low or intermediate probability of asthma. Chest X‑ray and specialist referral may be considered in any patient presenting atypically or with additional symptoms or signs.

3.12 Asthma management aims to control symptoms (including nocturnal symptoms and exercise-induced asthma), prevent exacerbations and achieve the best possible lung function, with minimal side effects from treatment. The British guideline on the management of asthma (2012) recommends a stepwise approach to treatment in both adults and children. Treatment is started at the step most appropriate to the initial severity of the asthma, with the aim of achieving early control of symptoms and optimising respiratory function. Control is maintained by stepping up treatment as necessary and stepping down when control is achieved. Management options include interventions with or without the use of drugs.

3.13 For most children and adults, asthma is monitored in primary care by routine clinical reviews on at least an annual basis. These reviews include (but are not limited to) assessment of the patient's symptom score (using a validated questionnaire), exacerbations, oral corticosteroid use, time off school or work, growth in children, inhaler technique and, in adults, lung function assessed by spirometry (PEF).