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Abstract
Background Identification of bacterial pathogens is paramount for prompt and effective treatment of respiratory exacerbations in children with cystic fibrosis (CF). This can be a challenge in non-expectorating patients as reliability of cough swabs (CS) is poor. More recently, cough plates (CP) have been reported to give high yields in some series. The aim of the study was to ascertain their effectiveness compared to CS and to assess the impact of cough strength on efficacy of CP.
Method Non-expectorating children with CF aged 3–16 years were recruited. Baseline data was recorded and peak cough flow measured. Specimens were obtained with CP and a cough swab in a randomised order and repeated at up to four clinic visits to obtain multiple measurements. Subjects completed a short questionnaire.
Results Number of subjects was 95, mean age 8.8±4.1 years, 45 males. Mean baseline % predicted FEV1 was 90.8±18. In total, 324 sets of specimens were collected. Pathogens were isolated in 18.2% of CS and 8% of CP. Agreement between the two specimens occurred in only 5.5% of cases. CP isolated pathogens on six occasions when the CS was negative while 40 CS were positive with a corresponding negative CP. Cough strength increased with age, and there was a trend towards older children isolating more pathogens on CP. However, this was not statistically significant. The majority of subjects preferred the CP.
Conclusions CP are less effective than CS in identifying respiratory pathogens in children with CF.
- Cystic Fibrosis
- Cough plates
- Cough swabs
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What is already known on this topic
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Isolation of bacterial pathogens is central to appropriate management of infection in patients with cystic fibrosis.
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Cough swabs can identify pathogens from the lower respiratory tract but often reflect the presence of upper airway commensal organisms.
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Cough plates have demonstrated equivalent sensitivity to sputum specimens in expectorating children with cystic fibrosis.
What this study adds
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Cough plates are less effective than cough swabs in the identification of bacterial pathogens in non-expectorating children with cystic fibrosis.
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Cough swabs should remain the procedure of choice for collecting specimens from non-expectorating patients.
Introduction
Progressive deterioration of respiratory function is the most common cause of morbidity and mortality in cystic fibrosis (CF),1 but more aggressive management of respiratory exacerbations has resulted in greatly improved outcomes. Isolation of bacterial pathogens is central to appropriate management of infection. Sputum samples accurately reflect lower respiratory pathogens.2 However, obtaining sputum from paediatric patients can be difficult and alternative strategies need to be employed for the non-expectorating patient. The most frequently performed investigation in this group is the cough swab or oropharyngeal swab. Organisms isolated from a cough swab may be representative of lower airway pathogens, but often reflect the presence of commensal organisms colonising the upper airway.3–5 Broncho alveolar lavage (BAL) is generally regarded as the gold standard of care but it is invasive, time consuming, costly, is usually performed under general anaesthetic in children and cannot readily be repeated.
More recently, cough plates have been reinvestigated as a sample collection method. Originally they were used in the diagnosis of pertussis but were superseded by per nasal swabs.6 The use of cough plates involves the patient coughing directly onto plates of blood, chocolate and Burkholderia cepacia-sensitive agar. The plate has a large surface area, and the technique is significantly less intrusive than performing a cough swab. A comparison of cough plates with cough swabs and sputum specimens in 31 expectorating CF patients showed that cough plates were significantly more sensitive than cough swabs and were equivalent to sputum specimens.7 A subsequent abstract confirmed the increased efficacy of cough plates compared to cough swabs in 131 non-expectorating children with CF8 although a further abstract demonstrated the opposite result in 48 children.9
Many questions remain regarding the use of cough plates in clinical practice. The primary issue is of their potential use in non-expectorating patients. Further questions include the possible relationship between cough strength and yield, and the earliest age at which it may be feasible to use this method.
The primary aims of this study were to compare the efficacy of cough plates and cough swabs in non-expectorating children with CF, to assess the strength of cough required to perform an effective cough plate, and to ascertain subjective opinions of the two methods of specimen collection.
Methods
Subjects were recruited from the CF clinic at the Great North Children's Hospital, Newcastle upon Tyne. Research ethics approval was granted by Trent research ethics committee. Inclusion criteria were a diagnosis of CF confirmed by two positive sweat tests and/or positive genotype, aged 3 years and over, ability to cough to command and inability to expectorate sputum. Once informed consent was obtained, baseline data were recorded. These included date of birth, sex, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), respiratory symptoms and current antibiotic usage.
Cough strength was measured by recording peak cough flow (PCF). This measure has previously been reliably demonstrated in neuromuscular patients.10 ,11 Subjects were asked to take a maximal inspiration and then cough forcefully into a tight fitting soft facemask attached to a Vitalograph 2120 handheld spirometer while sitting. This measurement was repeated three times and the best was recorded for analysis.
Following this, specimens were obtained with cough plates and a cough swab in a randomised order. The cough swab was performed by asking the subject to cough onto a cotton-tipped swab placed at the back of the mouth but not touching the posterior pharynx.4 To obtain the cough plates, subjects were requested to take a maximal inspiration and then to cough twice onto each of three cough plates (blood agar, chocolate agar and B cepacia selective medium) in random order. The plates were held by the investigator 5 cm from the individual's mouth. All specimens were taken by the specialist respiratory physiotherapist (NB). Each individual repeated this procedure at subsequent clinic visits, up to a maximum of four occasions. On completion of the study, they were requested to complete a short questionnaire asking their opinions and preferences regarding the two specimen collection methods.
Specimens were labelled and transferred to the microbiology laboratory for analysis immediately after the clinic had finished. Cough swabs were stored and transferred at room temperature, and plates were placed in a cool box as recommended. Cough swabs were plated onto Blood (BA), Chocolate bacitracin (CBAC) and B cepacia (BCEP) media. Culture plates from all specimens were then handled in the same manner. BA and CBAC were incubated at 37°C in CO2 and examined after 24 and 48 h. B cepacia cultures were incubated for up to 5 days at 30°. All possibly significant isolates were identified to species level using an automated identification system, and susceptibility testing was performed using standard methodology.
Statistical analysis
The number of CF patients attending the Great North Children's Hospital who were eligible for participation in this study was 124 (87 full care, 37 shared care). Following an initial power calculation accounting for repeated measures, a sample size of approximately 400 was estimated to provide 80% power to detect an effect size of approximately 20% for growth of bacterial pathogens at the 0.05 significance level. All cases who completed at least one study visit were included in the analysis. The statistical package used was Stata V.9.0. Means±SDs and percentages were calculated. Comparison of proportion of growth on cough swabs versus cough plates was analysed using the McNemar test of two proportions. The McNemar test was used as a secondary analysis to take into account the repeated measures on the same subjects. Cough strength was plotted in relationship to positive/negative cough plate results. Recruitment was stopped at 324 specimens following an interim analysis which demonstrated a significant difference between the two specimen collection methods.
Results
The number of candidates enrolled was 95 (45 males) and all completed the study. Mean age was 8.8±4.1 years. Lung function was completed by 68 of them. The remaining 27 were aged between 3 and 6 years, and were unable to provide reliable, repeatable results. Mean FEV1 (% predicted for age and height) was 90.9±18 (range 50–129), FVC 93.7±16.7 (range 61–140). A total of 50 subjects were colonised with Pseudomonas aeruginosa, the definition for colonisation being that the subject had isolated P aeruginosa on three occasions in their lifetime.
Totally, 324 sets of cough plates and cough swabs were collected: visit 1, 95; visit 2, 86; visit 3, 78; visit 4, 65. Overall, pathogens were isolated in 18.2% of cough swabs and 8% of cough plates p<0.05. Results for individual visits are illustrated in table 1.
Specimens with pathogens isolated at each visit (number and %)
Agreement between the two specimen types occurred in only 5.5% of cases. The number of cough plates that isolated pathogens when the corresponding cough swab was negative was six. However, 40 cough swabs were positive with a corresponding negative cough plate. In two cases, the cough plate grew different pathogens from the cough swab. Table 2 shows the pathogens isolated for each of the two specimen collection methods.
Number of positive isolates for cough plates and cough swabs
As seen in table 2, P aeruginosa was isolated from 31 cough swabs and 13 cough plates. There were nine new isolates in non-colonised patients, three were identified on both cough plates and cough swabs, and six were only cultured from the cough swab. The chronically colonised group was comprised of 50 subjects. P aeruginosa was isolated in 14 of these subjects on 23 occasions; once in seven subjects, twice in six subjects and on four occasions in one subject. The number of isolates for each specimen type were as follows: cough swab alone, 13; cough plate alone, 1; both, 9.
Pathogens were isolated from cough swabs in 24 (26%) symptomatic subjects and from cough plates in 9 (9.9%). Pathogens were isolated from 32 (13.7%) asymptomatic patients using cough swabs, and from 16 (6.9%) using cough plates. P aeruginosa was isolated from a cough swab but not on the corresponding cough plate on seven occasions in the symptomatic group, and this pattern occurred on nine occasions in the asymptomatic group.
PCF was recorded in 76 subjects. The remaining 19 subjects did not have a sufficiently strong cough to register on the Vitalograph. Mean values for PCF were 294.7±128.7 (range 69–642). Mean values were higher for males (325.4±137.9) than females (263.9±112.3) and increased with age. There was insufficient positive data to perform formal statistical analysis, although the trend suggests that positive isolates were obtained more frequently in older children with higher PCF.
The questionnaire results indicated that 84% of subjects preferred cough plates to swabs. The main reason cited was that cough plates were less invasive and traumatic for the patient.
Discussion
This study has demonstrated that cough plates are less effective than cough swabs for isolating bacterial pathogens from non-expectorating CF patients; this data therefore reiterates the findings of Orska et al9 but using a larger cohort of patients.
These findings are in marked contrast with those in the study by Maiya et al7 in expectorating patients. There are numerous possible explanations for these differences. The most likely are that sputum producers may actually expectorate sputum onto the plate while coughing, and that the airway load of bacterial pathogens may be higher in sputum producers than in non-expectorating patients.
In a previous study from the Brompton Hospital, pathogens were isolated from cough swabs in 8% of asymptomatic and 26% of symptomatic patients.4 In this study, there were positive cultures in 13.7% of asymptomatic and 26% of symptomatic subjects indicating some equivalence with our findings. Overall, pathogens were isolated in 18% of cough swabs which is slightly higher than the Equi study, but this is unlikely to be significant. Non-pathogenic organisms were more common on cough swabs, presumably representing oropharyngeal contamination. The method used to obtain the cough swabs was to avoid direct contact between the swab and the oropharynx as previously described.4 This can be difficult to achieve, especially in younger, less cooperative children. It has also been demonstrated that cough swabs can indicate upper airway colonisation with commensal organisms.3–5 As cough plates are not invasive, very few non-pathogenic organisms were found. The isolation of potentially pathogenic organisms from the upper airways is also a possibility. Haemophilus influenzae and pneumococci may also colonise the upper airways without causing symptoms. Therefore, when these organisms are isolated on a cough swab, good clinical judgement is required to make treatment decisions.
Early identification of P aeruginosa is vitally important to maximise the success rate of eradication therapy. In this study, six new isolates were found solely on the cough swab. It is of some concern that a significant proportion of new isolates would be missed if cough plates alone were used, as this would potentially delay early initiation of eradication regimes.
Mycobacteria are important pathogens in CF and do not readily grow on cough swabs. It is interesting to note that one was identified on a cough plate but not on the corresponding cough swab, reiterating the point that different bacteria can be identified by different methods.
We had hoped to study the relationships between cough strength and culture results. Unfortunately, too few positive cough plates were obtained to allow firm conclusions to be drawn. There was a trend towards higher bacterial yields in children aged over 10 years than in younger patients. This may support the theory that cough strength is important, but it could also be due to older children having more established lung disease and therefore being more likely to isolate bacterial pathogens. A larger study would be required to explore this question further.
Some children find cough swabs traumatic and they are generally disliked. This has been clearly shown in the questionnaire results by the overwhelming preference for cough plates. However, until an equally or more effective method of obtaining specimens is available, cough swabs continue to be necessary. It could be advocated that both methods are used. However, there would be definite cost implications and also added burden to the children.
A limitation of this study was the lack of comparison to the gold standard which is the BAL. As mentioned previously, this is invasive, costly, involves a general anaesthetic and would not have been easily repeatable. Another issue is that all the specimens were collected by one observer. This design was used to reduce the possibility of bias but potentially may not be transferable to clinical practice. Further work could be done to assess inter-rater reliability.
In conclusion, cough plates were less effective than cough swabs in the identification of bacterial pathogens in our regional paediatric CF centre. Cough swabs should remain the procedure of choice for collecting specimens from non-expectorating patients.
Acknowledgments
We are very grateful to Tony Carroll and the staff in the microbiology department at the Newcastle upon Tyne Hospitals NHS Trust for their assistance in analysing the specimens. Also to the anaesthetics department for the loan of face masks. Statistical advice was gratefully received from Tom Chadwick and Mark Pearce. Most importantly, we acknowledge the children and their families who participated in the study.
Footnotes
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Contributors NB was involved in the conception and design of the study, data collection, analysis of results and drafting of the manuscript. DS and COB contributed to the planning of the study, discussion of the results and reading and commenting on the draft manuscript.
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Competing interests None.
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Ethics approval Trent Research Ethics Committee.
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Provenance and peer review Not commissioned; externally peer reviewed.