In the UK one in five people have been diagnosed with a respiratory disease (Public Health England (PHE), 2015)— around 12 million people in total in 2013 (British Lung Foundation, 2016: 14). The true figure is likely to be higher, taking into account undiagnosed cases of respiratory diseases such as chronic obstructive pulmonary disease (COPD) (PHE, 2015). Lung disease is a major burden on UK health services resulting in over 700 000 hospital admissions each year. Improving diagnosis and disease management are important in the strategy to decrease both the societal burden and the personal burden borne by patients and carers (Kuprys-Lipinska and Kuna, 2014; PHE, 2015; British Lung Foundation, 2016).
Importance of sputum samples
The collection of sputum is one of the most common tests within respiratory medicine (Hickin et al, 2015). Sputum is (coughed up and spat out) salivary matter mixed with mucus or pus from the respiratory tract. Mucus is naturally made by the cells in the trachea and bronchial tubes and lines the airways to prevent harmful substances entering the lungs by keeping the airways moist, which prevents dust, viruses and bacteria from passing into the lungs (Preston and Kelly, 2017). If any substances do enter the lungs the cilia will attempt to remove them, enabling the individual to swallow the mucus or cough it out (Fahy and Dickey, 2010; Preston and Kelly, 2017). In chronic respiratory disease too much mucus is often produced causing the cells that produce the mucus to expand, resulting in limited airflow, breathlessness and cough, often impacting on ventilation and causing infection (Preston and Kelly, 2017; Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2019).
Sputum samples are important to confirm a respiratory tract infection and its sensitivities to antibiotics (Shepherd, 2017). A respiratory tract infection can be defined as any infectious disease involving the upper or lower respiratory tract, including a cold, tonsillitis/pharyngitis, laryngitis, acute rhinitis, acute bronchitis, bronchiolitis, pneumonia and tracheitis (National Institute for Health and Care Excellence (NICE), 2008). It can be difficult to diagnose respiratory infections, particularly in COPD patients, as symptoms are often longstanding, meaning sputum samples are vital to determine whether bacteria are present, particularly if the patient has a cough and sputum production is increased and purulent (Cukic, 2013; NICE, 2018a). Frequent and repeated cellular and airway inflammation driven by bacteria has significant pathophysiological effects and thus worsens clinical outcomes for patients (Beasley et al, 2012). As such, where lower respiratory tract infection is present sputum samples are important in guiding appropriate antibiotic therapy (Reychler, et al, 2016).
Understanding a patient's usual sputum production (colour, viscosity, amount) is important in assessment of patient symptoms, as changes from this baseline may identify infection (Lareau et al, 2015; Preston and Kelly, 2017). It is important to note amount, colour, consistency and odour when reviewing sputum (Hickin et al, 2015). See Figure 1 for different sputum colours (Murray et al, 2009).
Different types of sputum can indicate different conditions, for example, in asthma sputum contains high levels of eosinophils and is often yellow in colour without any infection being present (Hickin et al, 2015). Carcinomas can produce mucoid sputum if present at the alveolar cell level; however, all other bronchogenic carcinomas will not produce any (Hickin et al, 2015). Chronic bronchitis is associated with a chronic cough and sputum production (for the majority of days over a 3-month period) so this is vital to be aware of to aid diagnosis (Mayo Clinic, 2019). The type of sputum produced can also help identify the causes of pneumonia, tuberculosis, lung abscess, COPD, bronchiectasis, aspergillosis and cystic fibrosis (Nall, 2012; Hickin et al, 2015; Doe, 2017).
Sputum collection has helped improve understanding of chronic airways disease as it can identify the presence and type of bacteria, which can indicate the severity of airways disease aiding treatment and management options (Lacy et al, 2005). Frequent high neutrophil levels in sputum usually indicates advanced COPD (Chung, 2001; Kim and Nadel, 2004; O'Donnell, et al, 2004; Hoenderdos and Condliffe, 2013). Similar to patients with asthma a third of patients with COPD have raised eosinophil levels in their sputum (Singh et al, 2014).
Sputum sample collection
The most common type of sputum sample test is microscopy, culture and sensitivities (MC&S). This type of test detects any presence of pathogenic bacteria and guides antibiotic treatment. It can also confirm the effectiveness of commenced treatment (Shepherd, 2017). A sputum sample should be requested if an individual has an increased cough with purulent sputum, pyrexia and/or signs of systemic infection (Shepherd, 2017; GOLD, 2019). A sputum sample should be placed in a clean sputum pot, preferably first thing in the morning when the patient has cleared the mouth and throat of debris and taken a deep cough (Preston and Kelly, 2017; Shepherd, 2017). The sample can be collected at any point during the chest infection, but ideally it should be obtained before commencing antibiotic therapy (Centers for Disease Control and Prevention, 2017). It should be taken to the laboratory ideally within 1 to 2 hours of being produced (Nall, 2012). Therefore patients in secondary care settings need to be aware that they should inform health professionals as soon as sputum has been produced to allow this to happen. In primary care ideally family members should take the sample to the surgery and if there is a delay then the sample should be kept in the fridge. Health professionals also need to be aware of this guidance so samples are not delayed in reaching the laboratory.
Additional strategies to support sputum collection include inducing sputum through inhalation of nebulised hypertonic saline, transtracheal aspiration, bronchoscopy and bronchial washings, with the latter usually being used to confirm any malignancies (Hickin et al, 2015). It has been reported when completing bronchoscopies that at least 50% of COPD patients have high concentrations of bacteria in their lower airways during exacerbations (Sethi et al, 2002). However, it has also been noted that during bronchoscopies there can be contamination of the upper airway with bacteria if protocols are not rigorously followed, meaning this statistic could be disputed (Charlson et al, 2011; Segal et al, 2013).
Induced sputum provides key information regarding the inflammatory process of the airways (Weiszhar and Horvath, 2013). This type of sputum collection is more accurate than spontaneous sputum as it provides greater cell viability and reproducibility of cell counts (Lacy et al, 2005). Tangedal et al (2014) found that although there were differences between spontaneous and induced sputum samples, there is scope for both types of samples in medicine as both can provide key information. The main differences, when measured during a COPD exacerbation, were that tumornecrosis factor-alpha (TNF-a) was significantly higher in spontaneous samples than in induced samples, and in spontaneous samples from ex-smokers interleukin 18 (IL-18) and monokine induced by gamma interferon (MIG) were significantly higher compared with induced samples. Those spontaneous samples that were found to have haemophilus influenza (HI) in them were associated with lower levels of interleukin 6 (IL-6), not comparative with induced samples. Finally, MIG levels were lower in spontaneous samples with HI, the opposite of findings in induced samples (Tangedal et al, 2014). It needs to be decided which sample technique is appropriate when requesting a sample, but practicality needs to be considered and in practice induced sputum collection is an infrequent procedure.
Microscopy of sputum is inexpensive and simple (Nall, 2012). The only disadvantages found were some chest discomfort when obtaining the sample due to deep coughing. Certain tests, such as for tuberculosis, are different as they require expensive equipment and specially trained professionals, making them more expensive than general microscopy tests (TBFACTS, 2019). They also require large amounts of sputum to detect a positive sample as sensitivity is low, and often take several weeks to confirm (Acharya, 2013; Doe, 2017).
Bathoorn et al (2017) confirmed that a low number of sputum samples are requested in primary care. This could be the result of patients not supplying the sample if left with a sputum pot and/or access to transportation to drop the sample at the surgery (Alves et al, 2016). COPD guidelines state sputum collection is not routinely recommended in primary care for the routine management of an exacerbation; however, if an individual is admitted into hospital and/or sputum is purulent then a sample should be sent for MC&S testing (NICE, 2018a). Nonetheless it could be argued if more sputum samples were taken in primary care then this might prevent hospital admissions as correct antibiotic prescriptions could be made sooner (Bathoorn et al, 2017).
Under-use of sputum sampling is likely to contribute to high levels of inefficiencies through healthcare expenditure, including prolonged and potentially unnecessary hospital admission, while also prolonging and worsening clinical outcomes for patients (Bathoorn et al, 2017). This may be due to a breakdown in communication between health professionals (for example. presuming others have already requested one), a lack of knowledge regarding antibiotic policy or doctors using old sputum cultures to guide antibiotic therapy, especially in high-risk patients who have previously grown pathogens (Bathoorn, et al, 2017). Over use and inappropriate use of antibiotics are driving worldwide antibiotic resistance (Shallcross and Davies, 2014). Therefore it is critically important that antibiotic prescriptions are based on sputum culture results, especially in cases of recurrent COPD exacerbations (Bathoorn et al, 2017).
A study undertaken by Bathoorn et al (2017) found in 3638 sputum samples 50% of them showed no potential pathogen and therefore would not require antibiotics. Hickin et al (2015) claimed bacteria found in sputum are often resistant to common antibiotics and therefore it is important to request an antibiotic sensitivity test through MC&S testing. Consequently this would help towards antibiotic resistance as over-prescribing can cause antibiotics to lose effectiveness (NHS website, 2016). Brusse-Keizer et al (2009) and Laue et al (2015) argued that treating all exacerbations of COPD based only on purulent sputum would result in over use of antibiotics. NICE (2018b) guidelines state that antibiotics should be considered if sputum colour has changed and there is an increase in thickness or volume that is out of the ordinary for the patient.
Antibiotic stewardship
Antibiotic stewardship includes coordinated strategies that aim to improve antibiotic use resulting in enhanced patient outcomes, reduced antibiotic resistance and decreased healthcare costs (World Health Organization, 2019; Society for Healthcare Epidemiology of America, 2019). Antibiotic stewardship aims to offer the most appropriate antibiotic to patients with a bacterial infection and avoid using antibiotics in those cases where no bacteria is present (Bathoorn et al, 2017). It is recommended stewardship programmes are undertaken by employers to monitor individual prescribing practices and to ensure guidelines are being followed (NICE, 2015).
Antibiotics should only be considered for COPD patients if in addition to a positive sputum culture there are symptoms of dyspnoea, cough and increased sputum volume and change in sputum colour (Pauwels et al, 2001; Celli et al, 2004; O'Donnell et al, 2007; NICE, 2018a; GOLD, 2019). Bathoorn et al (2017) further argued that in the COPD patient, antibiotic prescribing should be withheld unless there is clinical indication of infection, a raised temperature (38°C and above) or no response to treatment after 2 to 4 days; however, sepsis must not be ruled out in the presence of these symptoms. Nonetheless GOLD (2019) argued that, when indicated, antibiotics should be given for 5-7 days to decrease recovery time and hospital length of stay and the risk of early relapse. The antibiotic needed will be influenced by the pathogen grown (Cukic, 2013). Bathoorn et al (2017) suggested sputum Gram stains can provide helpful information regarding the need for an antibiotic prescription. If a sample shows no indication of a single microorganism or copious potential pathogenic organisms then it is highly likely to be non-bacterial (van der Valk et al, 2004).
Once the sputum has been analysed in the laboratory the bacteria or fungi responsible can be confirmed and the appropriate antibiotics can be prescribed by either a doctor or nurse prescriber (Nall, 2012). Microbiologists and pharmacists also often play a part in the guidance and prescription of antibiotics following sputum collection.
Summary
This article has demonstrated the importance of sputum samples to aid diagnosis and treatment and how there is a need for larger samples to be taken. Several ways of obtaining samples have been presented and discussed. All health professionals have a duty to ensure antibiotic prescribing is a safe and effective treatment for the benefit of the patient, embracing the principles of antibiotic stewardship.