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The postnasal drip (PND) syndrome is often linked as a cause of chronic cough although this is disputed.
Objectives
We examined the effect of specific topical treatment of rhinosinusitis on cough in patients presenting with a chronic cough associated with a postnasal drip or ‘nasal catarrh’.
Methods
Patients presenting with a chronic cough and who complained of PND were enrolled and symptoms of PND and cough were assessed by questionnaire and by a capsaicin cough response. Rhinosinusitis was assessed by questionnaires, direct examination of the nose and by high-resolution computed tomography. In an open study, they were treated with fluticasone nasules, ipratropium bromide and azelastine nasal sprays for 28 days, after which they were re-assessed.
Results
Eighteen out of 21 patients completed the study. All patients reported having the presence of mucus in the throat. Mean cough score improved post-treatment (p<0.05), but there was no significant change in capsaicin cough sensitivity or nasal catarrh questionnaire score. There was improvement in anterior nasal discharge symptom scores (p=0.005) and in endoscopic nasal scores post-treatment (p<0.01), with a tendency to improved PND scores.
Conclusion
In a pilot open ‘real-life' study treatment targeted towards rhinosinusitis accompanying PND syndrome and chronic cough led to an improvement in cough. A randomised controlled study is now needed to confirm or refute these findings.
Chronic cough with a history of excessive sputum production. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.
PND refers to the sensation of nasal secretions at the back of the throat (or of a ‘drip’), often resulting in the need to clear the throat and is associated with nasal stuffiness or nasal discharge. Sometimes, the patient may describe the sensation of ‘something running down the back of the throat’. It is also often referred to as ‘nasal catarrh’ or ‘mucus in the throat’ by patients in the UK. The diagnosis of PND-induced cough is made by reviewing symptoms, physical examination, radiological findings and response to therapy.
Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines.
However, patients with PND syndrome often have features of rhinosinusitis, and it is therefore not implausible that this may be involved in causing nasal secretions at the back of the throat, leading to cough. The reasons why the dispute about PND and cough continues include the fact that previous studies on PNDS have not examined the link between abnormalities of the nose and sinuses with chronic cough, have not quantified the symptoms associated with PND and have not recorded the effect of treatment given specifically and topically to the nose and sinuses in these patients on chronic cough and the nasal mucosa.
Our own experience in the Cough clinic and Nose clinic at the Royal Brompton Hospital, London, UK, relating to the success of controlling cough by treating rhinosinusitis has been very variable. In addition, in our cohort of chronic cough patients, a smaller proportion were labelled as having the PND syndrome as causing their cough,
Chronic cough with a history of excessive sputum production. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.
We have examined in a pilot study the relationship between PND syndrome and cough by recruiting patients presenting with chronic cough and who also complained of PND, described as mucus in the back of the throat or as nasal catarrh, and observing the effects of local specific treatments applied to the nose and sinuses on the cough.
Methods
Study population
This study was designed as an open real-life study. Patients, aged between 18 and 75 years, were recruited from our cough clinic over a period of 6 months. All subjects had a persistent dry cough of at least 8 weeks' duration and experienced and reported the sensation of ‘mucus in the throat’. They had been investigated and treated with a standard protocol for the exclusion of asthma and gastrooesophageal reflux. Subjects who did not report ‘mucus in the throat’ were excluded, and none of the subjects were on treatment for rhinosinusitis at the time of inclusion into the study. Other exclusion criteria included bronchiectasis, chronic obstructive pulmonary disease (COPD), current smokers, glaucoma, history of hypersensitivity to any of the study medications and those on prolonged courses of oral or injectable corticosteroids. The study was approved by the Brompton, Harefield and National Heart and Lung Institute Research Ethics Committee, and all subjects gave informed consent to participate.
Study protocol
There were five study visits. At the first visit, subjects had skin prick tests to common aeroallergens, lung function tests and exhaled nitric oxide measurements. They completed Nasal Catarrh and Leicester Cough Questionnaires. They were asked to complete diary cards documenting the severity of their cough and nasal symptoms for two weeks prior to commencing the study medications. They underwent an ear, nose and throat (ENT) assessment and had a high resolution computed tomography (HRCT) scan of the nose and paranasal sinuses at Visit 2.
At the third visit, their pre-treatment diary cards were collected, and they were issued with diary cards for four weeks. The subjects had a capsaicin cough challenge and commenced their four-week treatment, consisting of topical nasal sprays of fluticasone nasules (400 μg once a day), ipratropium nasal spray (42 μg three times a day) and azelastine nasal spray (140 μg twice daily). The patients were reviewed at the end of the treatment period at Visit 4, when they completed nasal catarrh and Leicester Cough Questionnaires, and had repeat spirometric tests, exhaled nitric oxide measurements and a capsaicin cough challenge. Diary cards were collected. The final visit consisted of an ENT review and a nasal examination.
Questionnaires and diary cards
The Leicester Cough Questionnaire was used to assess the impact of chronic cough on the patients' quality of life.
Subjects completed daily diary cards on their cough and nasal symptoms for two weeks before the study treatment commenced and throughout the four-week treatment period. The mean daily score pre- and post-treatment was calculated. Cough symptoms were graded 0–5 (0=no cough; 1=cough for short period; 2=cough for than 2 short periods; 3=frequent coughing does not interfere with activities; 4=frequent coughing interferes with activities; 5=distressing cough most of the day). The presence/severity of an anterior nasal discharge and ‘mucous in the back of the throat’ were graded 0–3 (0=none; 1=mild; 2=moderate; 3=severe). The nasal catarrh questionnaire had 12 questions on nasal symptoms and was marked out of 24 with the higher the score, the more severe the symptoms.
Briefly, single-breath inhalations of sodium chloride (0.9%) and increasing doubling concentrations of capsaicin (0.977–500 μmol/L) from a breath-activated dosimeter were inhaled in succession. Coughs were counted for 1 min after each dose. The end-point was the concentration of capsaicin required to induce five coughs (C5), and the data was analysed as the log10C5.
ENT review
Patients attended the Nose clinic at the Royal Brompton Hospital. The postnasal space and pharynx was examined via nasal endoscopy, and the degree of rhinosinusitis scored (SD, IM & HS). The HRCT scan of the nose and sinuses was scored using the modified Lund–MacKay grading system.
Data are reported as mean±SEM. Statistical analyses were performed using GraphPad Prism 4. The Wilcoxon signed-rank test was used to analyse the difference between pre- and post-treatment symptom scores, endoscopic nasal scores and capsaicin cough challenge.
Results
Of the 21 patients enrolled, 18 (14 of female gender) completed the study. One subject was diagnosed with glaucoma after consenting to participate and was withdrawn prior to commencing treatment, the other two withdrew prior to visit 2. The mean age was 57 years (range 44–75). Four out of 18 subjects were atopic as assessed by one or more positive skin prick tests to common aeroallergens. All subjects had normal lung function (mean FEV1 was 92%±3.4% predicted) and their mean exhaled nitric oxide was 13±1.3 ppb. Although all subjects reported having ‘mucous in the back of the throat’, a third of them had not heard the term PND prior to the study.
The patients had a mean cough score of 3.19±0.34 prior to starting treatment, and a mean LCQ score of 11.4±1.01. The capsaicin logC5 concentration was 0.425±0.11. The subjects' mean anterior nasal discharge symptom score 1.75±0.20 and posterior nasal discharge score of 2.01±0.14.
At nasal endoscopy before starting treatment, 80% of subjects had a nasal discharge and a third had mucosal oedema. Twenty-seven percent of patients had crusting, and a third had a deviated septum. Six percent had nasal polyps. Eight out of 18 subjects had normal (clear) CT scans of their nose and sinuses, 8 had mucosal thickening in at least 1 sinus and 2 had at least one opacified sinus.
All patients reported taking their three topical treatments regularly and none reported any adverse events. At the end of the treatment period, five out of 18 patients reported a significant improvement in their cough symptoms. Two of the three patients without clinical evidence of PND at the time of examination reported an improvement in their cough after the treatment period.
There was a significant decrease in mean cough severity score post-treatment (Fig. 1) but no significant change in LCQ score overall (Fig. 2). There were no significant changes in exhaled nitric oxide, lung function or capsaicin cough sensitivity post-treatment (Fig. 3).
Figure 1Self-administered cough score and nasal catarrh questionnaire scores before (pre) and after (post) treatment of rhinosinusitis.
Figure 2Individual values for exhaled nitric oxide (panel A), lung function as FEV1% predicted (Panel B), Leicester cough questionnaire score (Panel C) and capsaicin cough sensitivity as log C5 (Panel D) before (pre) and after (post) treatment of rhinosinusitis. None of the parameters shows significant changes.
Figure 3Symptom scores for anterior and for posterior nasal discharge before (pre) and after (post) treatment of rhinosinusitis. There was significant improvement in anterior nasal discharge score (p=0.005), while the posterior nasal drip score was not changed (p=0.009).
There was also no significant change in nasal catarrh questionnaire scores (Fig. 1) and in PND symptom scores (p=0.09) (Fig. 3). However, there was a significant clinical improvement in anterior nasal discharge symptom scores (Fig. 3), accompanied by a significant improvement in endoscopic nasal scores post-treatment (Fig. 4), characterised by reduction in discharge and oedema.
Figure 4Endoscopic nasal scores (ENS) obtained by direct inspection of right and left nostril assessed before (pre) and after (post) treatment of rhinosinusitis. There was a significant improvement in both nostrils following treatment.
There was a significant correlation (p=0.002) between baseline LCQ score and baseline mean cough score (Fig. 5). There was no correlation between LCQ score and capsaicin C5, or between change in cough severity score and change in anterior or posterior nasal discharge scores.
Figure 5Correlation between baseline cough scores and Leicester cough questionnaire (LCQ) scores (r=0.75; p=0.002).
In this pilot study, we examined the effect of topical treatments for rhinosinusitis on the symptoms of postnasal drip and accompanying chronic cough in a cohort of patients with chronic cough as their main symptom. The treatments used were topical corticosteroids, and nasal applications of H2-antihistamines and anticholinergic nasal spray. No antibiotics or saline sprays were given. Overall, treatment was associated with a significant improvement in cough scores post-treatment that accompanied reductions in symptom scores for anterior nasal discharge, a non-significant reduction for postnasal discharge, and no changes in the nasal catarrh questionnaire, although direct inspection of the nasal passages showed improvement in the appearances of the nasal mucosa. We observed no significant changes in capsaicin cough sensitivity or the Leicester Cough questionnaire. Our data suggest that treating PND syndrome with a combination of topical corticosteroids, antihistamines and anticholinergic lead to a modest improvement in chronic cough although this requires confirmation in a randomised controlled study. At the end of our study, 28% of patients had reported an overall improvement in their cough scores following treatment but with no improvement in LCQ scores or capsaicin cough responses. In other studies of chronic cough, topical corticosteroids used as treatment of the primary condition associated with cough such as cough variant asthma or eosinophilic bronchitis have improved symptoms of cough or Leicester Cough Questionnaire scores.
To date, there are no controlled, double-blind studies looking at whether treating rhinosinusitis improves cough symptoms in patients with chronic cough. There have been a few open studies, which have looked at the outcome of treating ‘PND’ on cough, following a diagnostic and treatment algorithm, and these report a large degree of success in controlling cough. For example, one study using oral first generation antihistamine with a decongestant such as pseudoephedrine reported success in 59% of patients presenting with chronic cough and PND.
However, in these studies, there was no report of symptom measurement or examination of the rhinosinuses. It is also possible that improvements observed may have been due to the central effects of the orally administered drugs on the cough reflex. There have been trials involving the use of topical corticosteroids in allergic rhinitis, where improvements in cough symptoms have been demonstrated,
but these patients did not present primarily with chronic cough as a primary problem. The lack of correlation between changes in rhinitis scores and changes in cough symptom score indicate that the modest improvement in cough symptom score may not have resulted from the effect of the topical nasal treatments on rhinitis. It is possible that the topical treatments had somehow acted on the airway cough receptors.
When patients were recruited to this study, we found that up to one third had never heard of the term ‘PND’, although most knew about nasal catarrh or mucus in the throat. This term is much more widely used and familiar in the US.
The large geographical variation in reported incidence of PND is probably due to a combination of factors: differing definitions of PND being used in different populations, differing levels of awareness of the term and perception of symptoms by different populations, and a lack of a standardised method of measuring the symptoms. There has been a wide variation in the reported incidence of PND syndrome, with North American studies reporting higher rates than European studies. For example, in the United States, the reported incidence has ranged from 26% to 87% of patients with chronic cough,
The reason for the large differences in reported incidence rates is unlikely to be explained solely by the differences in the patient populations. There is some evidence to suggest that patients attending clinics in North America are more familiar with the term PND, and are therefore more likely to report it as a symptom than their UK counterparts.
Does ‘PND’ cause cough? This remains a contentious issue between otolaryngologists and respiratory physicians.
which is expectorated or swallowed with saliva. How a ‘postnasal drip’ may cause cough also remains debatable. It has been postulated that mucoid secretions may directly or indirectly (via inflammatory mediators) stimulate pharyngeal or laryngeal cough receptors. Pratter et al.
have reported that approximately 20% of patients with PND-associated with a chronic cough are not aware of a postnasal drip sensation at the back of their throat. Conversely, not all patients with ‘PND’ have cough. O'Hara et al.
found that out of 108 patients with purulent postnasal secretions attending a rhinology clinic, 21% complained of cough, which still remains a sizeable proportion.
Because the PND syndrome is only defined according to the presence of symptom(s), there have been moves to use alternative labels for this condition. In their latest clinical guidelines for the management of chronic cough, the American College of Chest Physicians recommend using the term upper airway cough syndrome (UACS), instead of PND syndrome,
Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines.
: this would be supported by our descriptive findings, plus the response to specific therapy. The response of cough to therapy was, however, small which questions whether rhinosinusitis was entirely responsible for reported cough in our patients. Cough may be related to laryngo-pharyngeal reflux rather than to any postnasal problems.
patients with a history of PND were enrolled into a double-blind study to receive rabeprazole or placebo for 90 days. The aim of the study was to look at the relationship between extra-oesophageal reflux and PND. Cough symptoms were evaluated as part of a nine-item scale with reflux symptoms. Compared with placebo, subjects receiving rabeprazole had a significant reduction in PND frequency and cough symptoms. It is unclear whether combination therapy of proton pump inhibitor with therapies for rhinosinusitis would work synergistically in reducing cough.
Although there are limitations to this ‘real-life’ study in view of the absence of a control group, we tentatively conclude that rhinosinusitis is present in many patients with the PND syndrome and that topical treatment directed towards rhinosinusitis may lead to improvement in associated chronic cough.
Competing interests
The authors declare that they have no competing interests.
Authors contributions
PM analysed the data and drafted the manuscript. HS participated in the design of the study, carried out ENT examinations, scored the CT scans and helped to draft the manuscript. JA and AT recruited subjects and collected the data. ISM participated in the design of the study. SRD participated in the design of the study, carried out ENT examinations and helped to draft the manuscript. KFC initiated the study, participated in its design, and drafted the manuscript.
Acknowledgements
We thank the staff of the outpatients of the Royal Brompton Hospital for their help.
References
Chung K.F.
Pavord I.D.
Prevalence, pathogenesis, and causes of chronic cough.
Chronic cough with a history of excessive sputum production. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy.
Chronic upper airway cough syndrome secondary to rhinosinus diseases (previously referred to as postnasal drip syndrome): ACCP evidence-based clinical practice guidelines.
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