Step-by-step diagnostic approach

Patients may present with a sub-acute cough, most commonly post-infection; however, most cases will be self-limiting. [2] Observation and, if required, symptomatic therapy are all that may be needed in these cases. Once the cough persists for longer than 8 weeks, further evaluation is indicated. Several validated tools of cough assessment are available. [12]

Pursuing the cause and resolution of chronic cough requires ongoing commitment to the patient. The approach to an individual patient with chronic cough may vary from full initial diagnostic evaluation for common associated diseases, to empirical but targeted therapy for common conditions known to cause chronic cough, with limited or no diagnostic efforts. [7] [13] Choice of the specific approach may be individualised, and depends on type and duration of symptoms, the patient's preference, and availability of resources. Limiting diagnostic testing, treating assumed aetiologies, and applying sequential empirical trials of therapy is most cost-effective, but leads to the longest time to disappearance of cough and may be associated with increased patient anxiety. [7] [14] [15] In practice, diagnostic and therapeutic processes are often applied simultaneously. It is best to involve the patient in choosing the best approach and to explain the expected duration and course of diagnostic and therapeutic trials.

History and examination

A detailed history is essential, with attention to time and clinical setting of onset, exacerbating factors, associated symptoms, prior history suggestive of atopic disease, a complete medical, smoking, drug, and exposure history, family history, and attention to what measures have already been tried, and to what effect. The history heavily influences the clinician's impression as to which (if any) of the 4 most common aetiologies (upper airway cough syndrome [UACS], asthma, gastro-oesophageal reflux disease [GORD], or non-asthmatic eosinophilic bronchitis [NAEB]) are most likely. A careful examination is, unfortunately, unlikely to inform the clinician regarding the commonest causes of chronic cough, but is essential for early detection of less common causes, such as bronchiectasis, interstitial lung disease, neoplastic disorders, or chronic infectious pulmonary diseases. Laboratory assessment of sputum production is a key factor in narrowing the differential, as it can indicate presence of an infectious cause. Although no specific history or physical examination findings are reliably associated with specific aetiology of chronic cough, they may direct further testing or therapeutic trials.

The symptoms and findings associated with the common causes (asthma, UACS, GORD, or NAEB) may direct further diagnostic evaluation towards confirming that cause.

Asthma may present with wheezing, chest tightness, or dyspnoea apart from paroxysms of cough, or exacerbation of cough by seasonal exposures, specific irritants, or non-specific respiratory irritants such as cold air, aromatic vapours, or dusty environments. In patients who do not ever wheeze, another cause should be considered. [7] There may be variability of symptoms, nocturnal exacerbation of cough, or a strong family history of asthma or atopic disease. [16] Cough-variant asthma, in which cough is the sole symptom, is present in a sub-group of patients. [8]

UACS is a clinical syndrome and diagnosis is based on the clinical picture (which includes frequent throat clearing, postnasal drip, nasal discharge, nasal obstruction, and sneezing) and response to therapy. [17] Potential causes of UACS include allergic rhinitis, perennial non-allergic rhinitis, post-infectious rhinitis, bacterial sinusitis, allergic fungal sinusitis, rhinitis due to anatomical abnormalities, nasal polyposis, rhinitis due to physical or chemical irritants, occupational rhinitis, rhinitis medicamentosa, and rhinitis of pregnancy. [17]

GORD may present with heartburn, dysphagia, acid regurgitation, and an associated cough with slouched posture. Suggestive symptoms may include cough on phonation, cough on rising from bed, or association with certain foods or with eating in general. [7] Reflux disease is clinically silent in up to 75% of cases. [18]

NAEB presents with a chronic, generally scantily productive or non-productive cough without prominent features of asthma or reliable cough triggers, although patients may complain of wheezing at times.

ACE inhibitor cessation

The cough from an ACE inhibitor may begin within days or months of onset of ACE inhibitor therapy. If use of ACE inhibitors is suspected as the cause, use should be stopped if at all possible. Diagnosis is then confirmed by the resolution of cough, usually within 1 to 4 weeks (although it may be up to 3 months). [19] Angiotensin receptor blocking agents do not appear significantly related to chronic cough symptoms.

CXR

A CXR should be obtained early in the evaluation of chronic cough. Although it is not diagnostic of the most common causes,View image findings may quickly divert the evaluation to causes of greater gravity. These include lung cancer,View imageView imageView imageView image pulmonary fibrosis,View image tuberculosis,View imageView image bronchiectasis,View imageView image, pneumonia,View imageView imageView image, aspiration,View image and sarcoidosis.View image

Choice of diagnostic testing or therapeutic trials

Following CXR, the choice of either diagnostic testing or therapeutic trials depends on the clinician's assessed probability of a specific aetiology and the patient's preferred approach. Unless the history, physical examination, and CXR indicate otherwise, efforts should be concentrated on one or more of the 4 most common causes (asthma, UACS, GORD, NAEB). For example, if the history is most suggestive of asthma, then spirometry and bronchoprovocation challenge testing would be the most appropriate first test. If this proves negative, NAEB should be considered. If UACS is suspected, a therapeutic trial aimed at resolving rhinosinusitis and reducing excessive secretions is indicated. If GORD is suspected, either a therapeutic trial or diagnostic testing may be employed (taking into account both the clinician's and patient's preferences).

Therapeutic trials

Therapeutic trials are selected based on clinical impression, at times supported by diagnostic testing. The patient's response to the trial must be assessed and the cough resolved before a given aetiology may be assigned with certainty. A partial response may indicate that more than one aetiology is in play. In this event, further testing and/or additional therapeutic trials may be indicated, while the partially successful therapy should be continued. Lack of a response requires reassessment both of suspected aetiology and of treatment adherence and effectiveness. High placebo effect has been reported in empirical trials in chronic cough. [20]

Empirical therapeutic trials may be undertaken sequentially (starting with the most likely aetiology first), with subsequent selections made according to patient response. Alternatively, trials may be undertaken simultaneously when multiple aetiologies are suspected from the outset, with subsequent sequential withdrawal of therapies once the cough is controlled. The following are considered:

1. UACS: failure of response to appropriate therapeutic trials should prompt a sinus CT and ENT referral, particularly if other aetiologies have been considered and deemed very unlikely.

2. Asthma or NAEB: failure of response to appropriate therapy should prompt careful evaluation for treatment adherence, anti-inflammatory effectiveness (measured by exhaled nitric oxide and peak-flow variability, as appropriate), and conditions that contribute to ongoing poor asthma control such as GORD, sinus disease, or ongoing allergen exposure.

3. GORD: failure of response to an appropriate therapeutic trial of 8 to 12 weeks should prompt confirmatory testing (if not already done), and careful assessment of effectiveness of acid suppression and/or other factors contributing to ongoing non-acid reflux.

Further diagnostic evaluation

If none of the 4 most common causes seem likely after thorough assessment, other tests to consider include:

1. High-resolution CT imaging of the chest to look for bronchiectasis (which does not always promote a productive cough)View imageView image or other structural disease (which may not show well on CXR).View imageView imageView image Chronic suppurative lung disease is diagnosed in patients with clinical symptoms of bronchiectasis but no radiographic evidence of bronchiectasis. [21]

2. Bronchoscopy to search for endobronchial pathology. View image

3. CT sinuses or nasendoscopy.

4. 24-hour oesophageal pH and/or impedance monitoring to rule out silent GORD.

5. Serum ferritin and iron, since iron deficiency has been associated with chronic cough. [22]

In addition, pulmonary and/or ENT consultation should be considered. In cases where the patient also has features of stridor, laryngospasm, or paradoxical vocal fold motion, early involvement of a speech pathologist is appropriate, since treatment directed at underlying causes may speed resolution of chronic cough as well. [23]