Samantha Decalmer

Acoustic Cough?Reflux Associations in Chronic Cough: Potential Triggers and Mechanisms

BACKGROUND & AIMS Central sensitization is thought to play a role in chronic cough and might explain the temporal association between cough and gastroesophageal reflux (GOR) in patients in whom non-GOR causes have been excluded. Using our novel simultaneous acoustic cough recording and impedance/pH monitoring technique, we aimed to explore this further by assessing such temporal associations and their relationship to the acidity, duration, and proximal extent of reflux and the presence of erosive disease and cough reflex sensitivity in unselected patients (ie, including non-GOR causes) with chronic cough. METHODS Twenty-four hour ambulatory acoustic cough monitoring with simultaneous impedance/pH recording was carried out in 71 unselected patients with chronic cough, aged 51-64 years (47 female). In addition, all patients underwent cough reflex sensitivity testing to citric acid, and 66 patients underwent gastroscopy. Temporal associations between cough and reflux were expressed using the symptom association probability. RESULTS Seventy percent of patients exhibited temporal associations, with 48% having a positive symptom association probability (SAP(R-C)) for cough preceded by reflux (mainly distal), 56% a positive symptom association probability (SAP(C-R (2 min))) for reflux preceded by cough, and 32% both. Moreover, SAP(R-C) positive patients had a more sensitive cough reflex (P = .03) but similar esophageal reflux exposure and erosive disease, together with similar prevalence of extraesophageal causes of cough compared with SAP(R-C) negative patients. Reflux immediately following cough was rare. CONCLUSIONS Cough temporally associates with reflux irrespective of proposed diagnoses, may be self-perpetuating in some patients, and is likely to be driven by central processes.

Chronic cough: how do cough reflex sensitivity and subjective assessments correlate with objective cough counts during ambulatory monitoring?

Background: Cough reflex sensitivity, subjective estimates of cough frequency and cough-related quality of life have been used to assess cough and monitor treatment responses. The relationships between these measures and objective cough monitoring remain unclear and the usefulness of subjective assessments remains questionable. Subjects: 62 patients with chronic cough (39 women) were studied. Mean age of patients was 54.9 (SD 12.2) years, with a median duration of cough of 5.5 (range 1–30) years. Methods: Cough reflex sensitivity testing (C5; citric acid) was performed in all patients before fully ambulatory day-time and night-time cough recordings. Patients scored the frequency and severity of their cough (Visual Analogue Scales (VAS) and 0–5 score) for each recording period and completed a cough-related quality-of-life questionnaire, Leicester Cough Questionnaire (LCQ). Ambulatory cough recordings were manually counted and reported in terms of cough seconds per hour (cs/h). Cough rates were log10 transformed for analysis. Results: The median time spent coughing was 11.36 (range 1.06–46) cs/h with median day rates of 15.59 (range 2–74.8) cs/h and median night rates of 2.94 (range 0–26.67) cs/h. An inverse relationship was seen between day cough rates and log10 C5 (r = −0.452, p⩽0.001). Subjective cough scores and visual analogue scales were only moderately associated with objective time spent coughing, with night-time being scores more strongly associated than day-time scores. The strongest correlation with objective cough frequency was cough-related quality of life (LCQ), (r = −0.622, p⩽0.001), mediated through the psychological domain. Conclusions: Subjective measures of cough and cough reflex sensitivity are only moderately related to objective time spent coughing, and hence cannot be used as surrogate markers for objective cough-frequency measurements. Cough-related quality of life (LCQ) is most strongly related to objectively counted cough, and may be a useful adjunct to objective measures in the assessment of cough.

Sex differences and predictors of objective cough frequency in chronic cough

Background: Women are consistently over-represented in specialist cough clinics and known to have a more sensitive cough reflex than men. Whether female sex and other patient characteristics are associated with higher cough rates is not known. A study was conducted to determine the predictors of objective cough frequency in patients presenting to a tertiary referral clinic with chronic cough. Methods: 100 subjects (65 women) of mean (SD) age 55.8 (11.0) years and median cough duration 4 years (IQR 2.0–10.0) with unexplained chronic cough completed flow-volume loops (mean (SD) forced expiratory volume in 1 s 103 (15.2)% predicted; forced expiratory flow (FEF50) 68.8 (24.1)% predicted), methacholine challenge (42% positive), citric acid cough reflex sensitivity (C5; 0.12 M (IQR 0.06–0.50)) and the Leicester Cough Questionnaire. 24-h ambulatory cough monitoring was performed in 86 subjects; manually counted coughs were quantified as the number of explosive cough sounds per hour. Results: Women coughed significantly more than men (geometric mean 16.6 coughs/h (95% CI 13.1 to 21.0) vs 9.4 coughs/h (95% CI 6.4 to 13.9), p = 0.01)). The cough reflex was also more sensitive in women than in men (median logC5 −0.9 M vs −0.6 M, p = 0.002), but cough-related quality of life was similar in women and men (12.0 (3.6) and 12.2 (3.2), respectively, p = 0.76). Linear regression analysis showed that 38.6% of the variation in cough rate was predicted by sex (p = 0.01), logC5 (p<0.001) and age (p = 0.002) but not lung function or bronchial hyper-reactivity. Conclusions: Ambulatory objective cough monitoring provides novel insights into factors modulating chronic cough. These findings suggest that effects of sex and age must be taken into account in the study of cough and when designing clinical trials testing novel antitussive agents.

How to quantify coughing: Correlations with quality of life in chronic cough

Different methods are used for quantifying coughing in sound recordings, but as yet no method has been shown to be more valid than any other. In the present study, the relationships between three different units of cough were examined and their ability to predict subjective ratings of cough and cough-related quality of life were evaluated. In total, 70 subjects (mean±sd age 55±11.7 yrs, 51 (73%) females) with chronic unexplained cough (median duration 4.8 yrs, interquartile range 2.5–10.1 yrs) performed fully ambulatory 24-h sound recordings, which were manually counted by trained observers and quantified by 1) explosive phases, 2) cough seconds and 3) cough epochs. Subjects also completed cough visual analogue scales (VAS) and the Leicester Cough Questionnaire (LCQ). All units of cough were strongly correlated; explosive phases and cough seconds correlated slightly more strongly than cough seconds with cough epochs or explosive phases with cough epochs. LCQ scores correlated moderately with explosive phases and seconds; epochs correlated slightly less well. Cough VAS scores showed a similar pattern. Explosive phases and seconds are interchangeable units of cough, moderately related to subjective measures and cough-related quality of life; epochs are a less satisfactory alternative.

Chronic Cough: Relationship Between Microaspiration, Gastroesophageal Reflux, and Cough Frequency

BACKGROUND Microaspiration is often considered a potential cause of cough. The aim of this study was to investigate the relationship between microaspiration, the degree and type of gastroesophageal reflux, and the frequency of coughing in patients with chronic cough. METHODS One hundred patients with chronic cough (mean [± SD] age, 55.8 years [± 11.0 years]; 65 women) and 32 healthy volunteers (median age, 43.5 years [interquartile range (IQR), 30-50.8 years]; 16 women) were recruited. Patients with chronic cough performed 24-h objective cough frequency with simultaneous esophageal impedance/pH monitoring and measurement of pepsin concentrations in sputum and BAL. Twelve healthy volunteers underwent bronchoscopy/BAL, and 20 underwent impedance/pH monitoring. RESULTS Patients with chronic cough had significantly more reflux episodes than healthy volunteers (median, 63.5 reflux episodes [IQR, 52.5-80.0] vs 59.0 [IQR, 41.8-66.0]; P = .03), although the absolute difference was small, and there was no difference in numbers of events extending into the proximal esophagus (median, 17.2% [IQR, 8.0%-26.0%] vs 20.3% [IQR, 5.1%-32.1%]; P = .36). BAL pepsin levels were also similar in chronic cough to control subjects (median, 18.2 ng/mL [range, 0-56.4 ng/mL] vs 9.25 ng/mL [range, 0-46.9 ng/mL]; P = .27). Sputum but not BAL pepsin weakly correlated with the number of proximally occurring reflux events (r = 0.33, P = .045) but was inversely related to cough frequency (r = −0.52, P = .04). Sputum pepsin was, therefore, best predicted by combining the opposing influences of cough and proximal reflux (r = 0.50, P = .004). CONCLUSIONS Proximal gastroesophageal reflux and microaspiration into the airways have limited roles in provoking chronic cough. Indeed, coughing appears to be protective, reducing pepsin concentration in the larger airways of patients with chronic cough.

A Novel Approach to Studying the Relationship Between Subjective and Objective Measures of Cough

BACKGROUND Currently, no data are available on the relationship between changes in objective and subjective measures of cough, the magnitude of change in cough frequency perceived by patients as clinically meaningful, or the sample sizes required to show significant changes in cough therapeutic trials. Because patients anecdotally report reductions in cough severity while undergoing esophageal testing, we aimed to address these issues by assessing objective and subjective measures of cough with and without an esophageal catheter. METHODS Twenty-four-hour cough monitoring was performed on two occasions, with and without esophageal impedance/pH monitoring in 62 patients with chronic cough (mean age 56.8 years [SD±10.8]; 43 women; median cough duration 3.3 years [interquartile range (IQR), 2.0-10.0]). Cough was assessed objectively measuring coughs per hour and subjectively using a numerical cough score and a visual analog scale (VAS), scored separately for day and night, and then averaged to represent each 24-h period. RESULTS Objective cough frequency was reduced by a median of 33.3% (IQR, -68.8% to -13.0%; P<.001) with the catheter. The averaged day and night cough scores and VAS scores also significantly decreased, but changes in these did not correlate with decreases in cough frequency. Sample-size calculations suggested that crossover designs using objective cough frequency may be preferable in therapeutic trials. CONCLUSIONS These observations provide useful information on the reduction in objective cough frequency scored as an improvement by patients with chronic cough and offer guidance for the design and powering of future therapeutic trials. TRIAL REGISTRY ISRCTN; No.: ISRCTN62337037; URL: http://www.controlled-trials.com.

Airway abnormalities at flexible bronchoscopy in patients with chronic cough

The algorithms utilised in the diagnosis of chronic cough advocate sequential investigations and treatment trials for asthma-like syndromes, post-nasal drip and gastro-oesophageal reflux disease; however, the role of bronchoscopy is unclear. In the present authors’ specialist clinic (North West Lung Centre Cough Clinic, Manchester, UK), flexible bronchoscopy is included in the diagnostic work-up of patients with chronic unexplained cough. In a retrospective review, the authors report on their experiences. Over an 18-month period, patients followed a diagnostic algorithm that included: chest radiography; pulmonary function; methacholine challenge; ear, nose and throat examination; and empirical reflux treatment. Where diagnosis remained elusive, bronchoscopy was performed. A total of 82 bronchoscopies were carried out for the sole indication of chronic cough. Patient age (mean±sd) was 54.9±11.22 yrs, with a median (range) cough duration of 5 (0.5–30) yrs. In nine (11%) subjects, a diagnosis was made on inspection or biopsy. These included seven cases of tracheobronchopathia osteochondroplastica (TPO), one case of elongated uvula and one case of endobronchial amyloidosis. All TPO patients had early changes, with a typical nodular appearance to the tracheal cartilage, without significant airway obstruction. These subtle changes could not have been predicted from less invasive procedures and would have been missed without bronchoscopy. Flexible bronchoscopy is indicated in persistent unexplained cough and may reveal contributing pathology.

Emergency oxygen therapy: from guideline to implementation

Educational aims To help readers understand the best way to use oxygen when they care for patients with medical emergencies. To encourage best practice in the use of emergency oxygen therapy. To raise awareness of the British Thoracic Society (BTS) guideline for emergency oxygen use. Summary Oxygen is the most commonly used drug in emergency medicine and when used judiciously in the treatment of hypoxaemia it undoubtedly saves life. However, oxygen is often used inappropriately and the dangers of over-oxygenation are unappreciated. In 2008, the first formal guidance on emergency oxygen use was produced by the British Thoracic Society. The guideline is objective, evidence based and peer reviewed, advocating safe use of oxygen by encouraging target saturation levels to be prescribed for each patient, based on a combination of what is believed to be safe and normal or near-normal. In the majority of patients a target saturation range of 94–98% is advised. The importance of recognition of patients at risk of type 2 respiratory failure is highlighted and, in such patients, a target saturation range of 88–92% is recommended.

PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study

BackgroundViral respiratory tract infection is the most frequent cause of acute cough and is reported at onset in about one third of patients with chronic cough. Persistent infection is therefore one possible explanation for the cough reflex hypersensitivity and pulmonary inflammation reported in chronic cough patients.MethodsBronchoscopic endobronchial biopsies and bronchoalveolar lavage cell counts were obtained from ten healthy volunteers and twenty treatment resistant chronic cough patients (10 selected for lavage lymphocytosis). A screen for known respiratory pathogens was performed on biopsy tissue. Chronic cough patients also underwent cough reflex sensitivity testing using citric acid.ResultsThere was no significant difference in incidence of infection between healthy volunteers and chronic cough patients (p = 0.115) or non-lymphocytic and lymphocytic groups (p = 0.404). BAL cell percentages were not significantly different between healthy volunteers and chronic cough patients without lymphocytosis. Lymphocytic patients however had a significantly raised percentage of lymphocytes (p < 0.01), neutrophils (p < 0.05), eosinophils (p < 0.05) and decreased macrophages (p < 0.001) verses healthy volunteers. There was no significant difference in the cough reflex sensitivity between non-lymphocytic and lymphocytic patients (p = 0.536).ConclusionsThis study indicates latent infection in the lung is unlikely to play an important role in chronic cough, but a role for undetected or undetectable pathogens in either the lung or a distal site could not be ruled out.Trials registrationCurrent Controlled Trials ISRCTN62337037 & ISRCTN40147207

S142 Investigating patterns in 24 hours of coughing

Introduction and Objectives Ambulatory 24 h cough monitoring is a relatively new technique, and so far few studies have investigated hourly variation in cough frequency. We analysed data from previous studies in three different disease groups to compare patterns throughout the day. Methods We studied chronic cough (duration>8 weeks) [n=70, median age 58 yrs (IQR 49–64), 67.1% female], acute cough in otherwise healthy volunteers (duration <3 weeks) [n=56, median age 22 yrs (IQR 21–25.5), 62.5% female] and physician diagnosed asthma [n=58, median age 58.5 yrs (IQR 52–67.8), 63.8% female]. Subjects wore a cough monitor (Vitalojak) for 24 h and median numbers of coughs in each hour were manually counted and plotted against the actual time of day. Results The asthmatic group had significantly lower total cough rates compared with the other groups (geometric mean 2.3 coughs/hr (SD±3.3); chronic cough 13.1 (±2.7); acute cough 8.9 (±2.63); p<0.001). Abstract S142 figure 1 shows the median coughs in each hour of the day (interquartile ranges). The chronic and acute cough groups show a very similar cough frequency and pattern, with two peaks during the daytime, despite substantial variability. The asthma group show a similar pattern but with much lower counts. For all diagnosis coughing practically ceases overnight.Abstract S142 Figure 1 Conclusions These data suggest that cough frequency in acute and chronic cough are remarkably similar, implying similar mechanisms may be driving coughing in these conditions, unlike in asthma where cough frequency is much lower. However all groups show similar fluctuations in hour to hour pattern of daytime cough and effective suppression of coughing during sleep, indicating behaviour has an important influence.