Current Respiratory Medicine Reviews - Volume 7, Issue 1, 2011

Full text available.

Full text available.

Chronic cough is defined as that lasting for more than eight weeks and is known to have a prevalence of around 10% in the community. Smokers have a much higher prevalence of cough than non smokers. Women have a higher prevalence of cough and have a more sensitive cough reflex as compared to men. Asthma and related syndromes, post nasal drip syndrome and gastro-oesophageal reflux disease have been thought to be the cause of chronic cough in a majority of cases. It has been recently suggested that chronic cough is a distinct clinical entity comprising of chronic cough with cough hypersensitivity. This has been termed the cough hypersensitivity syndrome.

Cough is one of the commonest symptoms of medical importance. The mechanism whereby this protective reflex, vital for the integrity of the airway becomes excessively stimulated has recently been elucidated. The tickly sensation which provokes the urge to cough is invested in a series of nococeptors, which become upregulated in pathological states. In both acute and chronic cough, hypersensitivity to noxious stimuli can be objectively demonstrated. Members of a class of ion channels of the Transient Receptor Potential family act as irritant receptors responding to a wide variety of stimuli. The archetypal receptor, TRPV1 is stimulated by heat, acid, and the pungent extract of peppers, capsaicin. TRPV1 is upregulated by inflammatory mediators. Over expression and agonist induced increase in opening probability of the ion channel leads to increased sensitivity in the upper airway. The related TRPA1 is co-localised with TRPV1 and responds to a wide range of environmental stimuli through non-specific binding. It is likely that the combination of these two receptors is responsible for the almost universal complaint from patients with chronic cough of exquisite sensitivity to previously innocuous stimuli. The term, the Cough Hypersensitivity Syndrome has been coined to encapsulate the clinical manifestations of this up-regulation which occurs in the majority of patients presenting to the cough clinic.

The most important factor in evaluating patients with chronic cough is the clinician's assessment. This can either suggest the diagnosis or direct investigations as needed. All patients with chronic cough should have a chest radiograph as well as a spirometric examination. The common causes of cough not associated with obvious respiratory disease include asthma and related syndromes, gastro-oesophageal reflux and Post Nasal Drip syndrome. Specialised investigations which may help to establish the diagnosis include broncho-provocation testing, induced sputum cytology, oesophageal manometry, 24-hour oesophageal pH monitoring, computed tomography (CT) and fiberoptic bronchoscopy. Systematic protocols with high diagnostic yields have been described to assess chronic cough. However if there is no ready access to investigations, therapeutic trials targeting the likely cause of cough are justified.

Cough is one of the commonest symptoms of medical importance with significant physical and psychosocial morbidity associated with it. The differential diagnosis of cough is very extensive and it is extremely important to investigate this symptom in a systematic manner to accurately diagnose the cause. Furthermore, the multi-factorial etiology of cough in respiratory diseases should not be ignored while managing this group of patients. In this review, we discuss the relationship of cough with certain respiratory disorders including airways and lung parenchyma. Moreover, the association of cough with autoimmune diseases, lung malignancy and obstructive sleep apnea is also reviewed.

Gastro-esophageal reflux disease (GERD) is a highly prevalent disorder which has been implicated in the pathophysiology of chronic cough. However there is much uncertainty as to the precise clinical association between the two. Despite this clinicians frequently consider GERD as an important aggravating factor and often consider trials of antireflux therapy without much evidence base. In this article we aim to summarise the existing literature on definition, epidemiology and clinical presentation of GERD and cough, highlighting current thinking on the pathophysiological and mechanistic association between gut and lung and its relevance to GERD associated cough. In addition we aim to discuss current approaches to the evaluation of patients with suspected reflux cough and how ‘state of the art’ and emerging technologies can more accurately identify such patients and in particular those most likely to benefit from treatment. Finally we provide a review of a number of trials of medical and surgical therapy in GERD associated cough and debate on some of the pertinent issues surrounding efficacy and safety of such treatment.

Cough sounds are readily identifiable by the human ear and therefore have the potential to be objectively quantified for the assessment of this common symptom. In recent years several systems for objectively measuring cough in ambulatory patients have been developed. Such objective measures are already providing insights into the mechanisms underlying coughing and the efficacy of novel and established anti-tussive agents. However, further development and validation is required to achieve accurate, fully automated cough detection systems applicable to large clinical trials and clinical practice. The aim of this review is to describe current cough recording and detection technologies, how these techniques have been applied in clinical studies and potential future developments.

Chronic cough seems more common in women than men. The mean ratio of female to male patients with chronic cough is 2.1 (95% CI, 1.6-2.4). Many large population-based studies have clearly demonstrated that females are more likely to suffer from angiotensin-converting enzyme (ACE)-inhibitors induced cough. When small sized cohort studies on chronic cough are reviewed, the mean ratio of female to male patients is 2.5 (95% CI, 1.7-3.3) in patients with gastro-esophageal reflux (GER) associated cough, 3.6 (95% CI, 1.5-5.8) in patients with atopic cough, 1.6 (95% CI, 0.8- 2.5) in eosinophilic bronchitis without asthma, 2.6 (95% CI, 1.8-3.4) in adult cough variant asthma and 1.9 (95% CI, 0.8- 4.7) in childhood cough variant asthma. Thus, it is likely that females are more likely to suffer from chronic cough, especially ACE-inhibitor-induced cough, GER associated cough, atopic cough and probably eosinophilic bronchitis without asthma, all of which are characterised by increased cough reflex sensitivity. In addition, female healthy volunteers have increased cough reflex sensitivity to inhaled capsaicin.

Cough is the most common complaint for which patients seek medical attention. Cough variant asthma (CVA) is a form of asthma, which presents solely with cough. CVA is one of the most common causes of chronic cough. More importantly, 30 to 40% of adult patients with CVA, unless adequately treated, may progress to classic asthma. CVA shares a number of pathophysiological features with classic asthma such as atopy, airway hyper-responsiveness, eosinophilic airway inflammation and various features of airway remodeling. Inhaled corticosteroids remain the most important form of treatment of CVA as they improve cough and reduce the risk of progression to classic asthma most likely through their prevention of airway remodeling and chronic airflow obstruction.

Preoperative assessment of a patient for the development of perioperative pulmonary complications is an important step in the risk reduction strategy of a patient undergoing elective surgery. The incidence of perioperative pulmonary complications and its effect on patient morbidity, mortality, and costs associated with hospital stay is just as high as that of cardiac complications. A multitude of modifiable and non-modifiable patient and procedure related risk factors are associated with perioperative pulmonary complications. Few clinical interventions including lung expansion maneuvers such as incentive spirometry and continuous positive airway pressure have been proven to be effective in the prevention of perioperative pulmonary complications, although the evidence base is limited by the lack of well designed randomized controlled trials. Given the ramifications of perioperative pulmonary complications it is imperative that providers involved in the perioperative care of patients undergoing elective surgery be cognizant of risks and management strategies of such complications. Risk modifying interventions should be introduced where applicable and alternate therapies should be considered when such risks are insurmountable.

Chronic medical conditions occur in more than half of the patients with COPD. They contribute to COPDrelated hospitalizations and they have been shown to prolong length of stay in patients with COPD. The presence of COPD can adversely impacts patients admitted to hospital with other conditions including pneumonia. Cardiovascular diseases are the leading causes of death in patients with COPD. Pharmacological treatment of COPD may adversely affect heart disease and diabetes. Recent studies highlight systemic morbidity with use of inhaled medications. Pulmonary hypert Musculoskeletal dysfunction, a systemic manifestation of COPD, contributes to exercise limitation. Osteoporosis occurs in patients with COPD even independent of oral steroid use. Gastro esophageal reflux symptoms are more common in patients with an FEV1 < 50%. Mortality is higher with poor glycemic control during a COPD exacerbation. Systemic inflammation in COPD is mediated by IL-6, IL-8, CRP and TNF α with the latter two contributing to anemia. CRP levels in COPD patients are associated with poor quality of life, reduced exercise endurance and correlate inversely with the 6 minute walk test. Clinicians needs to be aware of these co-morbidities and must evaluate their COPD patients accordingly. Early intervention can decrease intensity of the co-morbidity and improve quality of life in COPD patients.