Alyn H. Morice

The diagnosis and management of chronic cough

Fig. 1.— nOverview of the evaluation of chronic cough in an adult. ACE-I: angiotensin converting enzyme inhibitor; PEF: peak expiratory flow; PNDS: post-nasal drip syndrome; GORD: gastro-oesophageal reflux disease.nnnnnnFig. 2.— nTherapeutic algorithm. ACE: angiotensin-converting enzyme; GORD: gastro-oesophageal reflux disease.nnnnnnFig. 3.— nInvestigational algorithm. CT: computed tomography.nnnnnnFig. 4.— nDiagnostic algorithm for the approach to children with chronic cough. ENT: ear, nose and throat; PFT: pulmonary function testing; BAL: bronchoalveolar lavage; CT: computed tomography; tbc: total blood count; CMV: cytomegalovirus; PCR: polymerase chain reaction; MRI: magnetic resonance imaging; NO: nitric oxide; BHR: bronchial hyperresponsiveness.nnnnnnCONTENTSnnnnChronic cough, here defined as a cough of >8 weeks duration, is a common and frequently debilitating symptom 1, 2 that is often viewed as an intractable problem. However, theexperience of specialist cough clinics is that a very high success rate, in the order of 90%, can be achieved (tableu20051⇓) 3–15. The key to successful management is to establish a diagnosis and to treat the cause of cough. Truly idiopathic cough is rare and misdiagnosis common, particularly because of the failure to recognise that cough is often provoked from sites outside the airway. These guidelines aim to distil the lessons from these reports and provide a framework for a logical care pathway for patients with this highly disabling symptom.nnView this table:nnTable 1— nCommonest causes of chronic cough in patients investigated in specialist clinicsnnnnThere are three common causes of chronic cough that arise from three different anatomical areas. This varied presentation explains the major reason for the success of multidisciplinary cough clinics compared with general clinics 16. As asthma, reflux and rhinitis are the realms of different specialists who have little experience in the diagnosis of conditions outside their expertise, a patient with chronic cough may not undergo full evaluation. This problem is exacerbated by the frequently atypical presentation of …

Recommendations for the management of cough in adults

### 1.1 BackgroundnnPatients with cough frequently present to clinicians working in both primary and secondary care.1,2 Acute cough, which often follows an upper respiratory tract infection, may be initially disruptive but is usually self-limiting and rarely needs significant medical intervention. Chronic cough is often the key symptom of many important chronic respiratory diseases but may be the sole presenting feature of a number of extrapulmonary conditions, in particular upper airway and gastrointestinal disease. Even with a clear diagnosis, cough can be difficult to control and, for the patient, can be associated with impaired quality of life.3,4 Sessions dedicated to cough at respiratory meetings are popular, suggesting that the pathophysiology, evaluation, and successful treatment of cough remain topics of keen interest to many medical practitioners.nn### 1.2 Need and purpose of BTS recommendations on the management of coughnnThe American College of Chest Physicians (ACCP) and the European Respiratory Society (ERS)5,6 have each endorsed their own set of guidelines on the management of cough; however, criticism7 of their content and breadth suggest the need for further concise recommendations. The British Thoracic Society guidelines cover not only chronic cough but also acute cough and the organisational issues of cough clinics. International differences in delivery of respiratory health care and management strategies support the notion that such guidelines would be desirable. The British Thoracic Society Standards of Care Committee agreed to the development of a Working Group tasked with the job of producing a set of guidelines for the management of cough with the following key objectives:

NADPH oxidase: a universal oxygen sensor?

NADPH oxidase is classically regarded as a key enzyme of neutrophils, where it is involved in the pathogenic production of reactive oxygen species. However, NADPH oxidase-like enzymes have recently been identified in non-neutrophil cells, supporting a separate role for NADPH-oxidase derived oxygen species in oxygen sensitive processes. This article reviews the current literature surrounding the potential role of NADPH oxidase in the oxygen sensing processes which underlie hypoxic pulmonary vasoconstriction, systemic vascular smooth muscle proliferation, carotid and airways chemoreceptor activation, erythropoietin gene expression, and oxytropic responses of plant cells.

Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis

Background: It has been proposed that the pH of airway lining fluid may regulate the fractional exhaled concentration of nitric oxide (FeNO) in respiratory disease. Methods: FeNO, exhaled breath condensate (EBC) pH, and EBC concentrations of nitrite plus nitrate (NO2/NO3) were compared in 12 subjects with stable asthma, 18 with stable cystic fibrosis (CF), and 15 healthy control subjects. Eight of the CF patients were studied on a separate occasion at the start of a pulmonary exacerbation. Results: FeNO was significantly greater in asthmatic subjects than in control subjects (mean 35 v 9 ppb, p<0.001). EBC pH, however, was similar in the asthmatic and control groups (median 5.82 v 6.08, pu200a=u200a0.23). Levels of NO2/NO3 were on average higher in EBC samples from asthmatic subjects, but the difference was not significant. In patients with stable CF both the FeNO (mean 4 ppb, p<0.001) and EBC pH (median 5.77, pu200a=u200a0.003) were lower than in the control group. Levels of EBC NO2/NO3 (median 29.9 μM; pu200a=u200a0.002) in patients with stable CF, in contrast, were significantly higher than in control subjects. During CF exacerbations, EBC pH was further reduced (median 5.30, pu200a=u200a0.017) but FeNO and NO2/NO3 were unchanged. Conclusions: These findings demonstrate a dissociation between EBC pH and FeNO in inflammatory airways disease.

Evaluation of impulse oscillation system: comparison with forced oscillation technique and body plethysmography

To the Editor: nnWe read with interest the study by Hellinckx et al. 1, comparing the techniques of impulse oscillation, forced oscillation and body plethysmography. The impulse oscillation system (IOS) was recently introduced by Jaeger (IOS Enrich Jaeger, Hoechberg, Germany) and its clinical potential is due to its relatively easy acquisition of data. Subjects perform tidal breathing in the upright position without any forced expiratory manoeuvres. This method could therefore potentially acquire broad usage, especially among patients with poor coordination. However, our limited experience with IOS suggests that its wider utilization will be problematic. Conversely, body-box plethysmography is an established method that …

The automatic recognition and counting of cough

BackgroundCough recordings have been undertaken for many years but the analysis of cough frequency and the temporal relation to trigger factors have proven problematic. Because cough is episodic, data collection over many hours is required, along with real-time aural analysis which is equally time-consuming.A method has been developed for the automatic recognition and counting of coughs in sound recordings.MethodsThe Hull Automatic Cough Counter (HACC) is a program developed for the analysis of digital audio recordings. HACC uses digital signal processing (DSP) to calculate characteristic spectral coefficients of sound events, which are then classified into cough and non-cough events by the use of a probabilistic neural network (PNN). Parameters such as the total number of coughs and cough frequency as a function of time can be calculated from the results of the audio processing.Thirty three smoking subjects, 20 male and 13 female aged between 20 and 54 with a chronic troublesome cough were studied in the hour after rising using audio recordings.ResultsUsing the graphical user interface (GUI), counting the number of coughs identified by HACC in an hour long recording, took an average of 1 minute 35 seconds, a 97.5% reduction in counting time. HACC achieved a sensitivity of 80% and a specificity of 96%. Reproducibility of repeated HACC analysis is 100%.ConclusionAn automated system for the analysis of sound files containing coughs and other non-cough events has been developed, with a high robustness and good degree of accuracy towards the number of actual coughs in the audio recording.

Investigation and management of chronic cough using a probability-based algorithm

Chronic cough is a common and distressing symptom. A novel algorithm has been developed for the management of chronic cough, in which an assessment of clinical probability of disease determines the need to proceed to investigation. In this study, the performance of this algorithm in clinical practice was prospectively evaluated. A total of 131 consecutively referred patients (86 females) whose principal presenting symptom was a cough of duration >8u2005weeks were studied. Their age (median (range)) was 60 (16–88)u2005yrs and cough duration 5.9 (0.2–65)u2005yrs. A cause of cough was established in 93% of cases. The most frequent diagnoses were asthma (24% of cases), gastro-oesophageal disease (22%), post-viral cough (8%), bronchiectasis (8%) and interstitial lung disease (8%). Primary pulmonary disease was significantly more likely in patients with a productive cough and in patients with an abnormal chest radiograph. Only a small proportion (<8%) of patients had multiple causes of cough. The probability of treatment started on the basis of a high clinical suspicion of either asthma, gastro-oesophageal disease or rhinitis being successful was 74%. Overall, 26% of the patients were managed successfully without the need for any form of investigation other than chest radiography and spirometry. Use of the algorithm resulted in identification of the cause of cough and successful treatment in the large majority of cases. It is concluded that this protocol has the potential to improve management by providing a structured approach, reducing the number of investigations performed, and minimising unnecessary delays in treatment.

Cough Hypersensitivity Syndrome: A Distinct Clinical Entity

We postulate that most patients with chronic cough have a single discrete clinical entity: Cough Hypersensitivity Syndrome. We constructed a questionnaire that elicits the major components of the syndrome. Here we describe the validation of this questionnaire. Following iterative development, the Hull Airway Reflux Questionnaire (HARQ) was administered to patients and normal volunteers. It is self-administered and comprises 14 items with a maximum score of 70. Unselected patients were recruited sequentially from the Hull Cough Clinic. Preclinic questionnaires were compared with those obtained at the clinic. Responsiveness was assessed 2xa0months after the clinic visit. One hundred eighty-five patients and 70 normal volunteers were included in this study. There was a marked difference in HARQ scores between patients with chronic cough and normal volunteers. The sensitivity (94%) and specificity (95%) of the HARQ was high, with an area under the ROC curve of 0.99. All items of the scale significantly correlated positively with others in the scale and with the total score. On repeatability testing using Cohen’s kappa with quadratic weights, significant agreement was noted for all items. Good correlation was observed between the total scores (rxa0=xa00.78). The questionnaire was also responsive to treatment; the minimum clinically significant change was estimated to be 16 points. We have demonstrated the HARQ to have good construct and criterion validity. It is both reproducible and responsive to change. It can be used as a diagnostic instrument and demonstrates that chronic cough represents a single coherent entity: Cough Hypersensitivity Syndrome.

Abnormal oesophageal motility in patients with chronic cough

Background: Although gastro-oesophageal reflux is a recognised cause of chronic cough, the role of oesophageal dysmotility is unknown. The aim of this study was to determine the prevalence of abnormal oesophageal motility in a selected group of patients with chronic cough. Methods: Oesophageal manometry and 24 hour pH monitoring were performed in 43 patients with chronic cough, 34 of whom had symptoms suggestive of gastro-oesophageal reflux. Comparative manometric measurements were made in 21 healthy subjects. Results: Nine patients with chronic cough had normal manometry and 24 hour pH. Of the remaining 34 patients, 11 (32%) had abnormal manometry alone, five (15%) had abnormal 24 hour pH monitoring alone, and in 18 (53%) both tests were abnormal. Only one patient in the control group had manometric abnormalities. Conclusions: These results point to a previously unrecognised high prevalence of abnormal oesophageal manometry in patients presenting with chronic cough. Oesophageal dysmotility may therefore be important in the pathogenesis of cough in these patients.

Antitussive Drugs—Past, Present, and Future

Cough remains a serious unmet clinical problem, both as a symptom of a range of other conditions such as asthma, chronic obstructive pulmonary disease, gastroesophageal reflux, and as a problem in its own right in patients with chronic cough of unknown origin. This article reviews our current understanding of the pathogenesis of cough and the hypertussive state characterizing a number of diseases as well as reviewing the evidence for the different classes of antitussive drug currently in clinical use. For completeness, the review also discusses a number of major drug classes often clinically used to treat cough but that are not generally classified as antitussive drugs. We also reviewed a number of drug classes in various stages of development as antitussive drugs. Perhaps surprising for drugs used to treat such a common symptom, there is a paucity of well-controlled clinical studies documenting evidence for the use of many of the drug classes in use today, particularly those available over the counter. Nonetheless, there has been a considerable increase in our understanding of the cough reflex over the last decade that has led to a number of promising new targets for antitussive drugs being identified and thus giving some hope of new drugs being available in the not too distant future for the treatment of this often debilitating symptom.