Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA). Summary of an updated position statement on chronic cough in Australia

Marchant, Julie M; Chang, Anne B; Kennedy, Emma; King, David; Perret, Jennifer L; Schultz, Andre; Toombs, Maree R; Versteegh, Lesley; Dharmage, Shyamali C; Dingle, Rebecca; Fitzerlakey, Naomi; George, Johnson; Holland, Anne; Rigby, Debbie; Mann, Jennifer; Mazzone, Stuart; O'Brien, Mearon; O'Grady, Kerry‐Ann; Petsky, Helen L; Pham, Jonathan; Smith, Sheree MS; Wurzel, Danielle F; Vertigan, Anne E; Wark, Peter

doi:10.5694/mja2.52157

Topics

Statistics, epidemiology and research design

Respiratory tract diseases

Health occupations

General medicine

Abstract

Introduction: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation.

Main recommendations: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x‐ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada‐full‐position‐statement.

Changes in management as a result of this statement:

Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended.
High quality evidence supports the use of child‐specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults.
Red flags that indicate serious underlying conditions requiring investigation or referral should be identified.
Early and effective treatment of chronic wet/productive cough in children is critical.
Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted.
If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic.

Cough is a common condition leading to clinical consultation and results in significant health care costs. Guidelines seek to standardise and assist in diagnosis, investigation and management of cough.1,2 Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA) is an updated Australian position statement on the clinical assessment and management of chronic cough that highlights the burden of chronic cough, including the disproportionate burden in our First Nations population. We provide recommendations for initial assessment of chronic cough in clinical practice, including red flags in history and examination, and CICADA diagnostic management algorithms for use in paediatrics (Box 1) and adults (Box 2). As there is high quality evidence that the common aetiologies of chronic cough in children and adults are not the same, we discuss the management of paediatric and adult chronic cough separately.3

Method

CICADA was developed by a multidisciplinary expert committee that convened to undertake a systematic literature review and discuss updated recommendations. A total of 6395 articles were screened and 277 new studies since 2010 (the previous CICADA update)4 were included in the updated full statement (Box 3 provides details of the guideline development process). Throughout the position statement (in the main text and in the box summarising the recommendations and their level of evidence and strength), the GRADE of evidence6 refers to evidence of the efficacy of treatment recommendations for cough in association with the respective conditions. The full statement can be found at https://lungfoundation.com.au/resources/cicada‐full‐position‐statement. We plan to update the statement every 2 years.

Burden of chronic cough

In 2015, the prevalence of chronic cough in adults was estimated to be 9.6% (95% CI, 7.6–11.7%) globally,7 and 8.8% in Australia.8 The prevalence of chronic cough gradually increases to peak in the sixth decade9 and has been estimated to occur in 3% of never smokers, 4% of former smokers and 8% of current smokers.10 Overall, chronic cough presents more commonly in middle‐aged women.2

There are limited Australian studies on population prevalence of chronic cough in children.11 In a recent study of Australian children presenting to emergency departments, 7.5% had chronic cough, and 20–23% had persistent cough at day 28 irrespective of duration of cough on presentation.12 The prevalence of chronic wet cough in children living in Indigenous communities is higher (around 13%).13

First Nations Australians are disproportionately affected by conditions that present with chronic wet cough, such as protracted bacterial bronchitis and bronchiectasis. The mortality difference between First Nations and non‐First Nations Australians with bronchiectasis is about 22 years.14 In 180 First Nations children aged < 5 years presenting to primary care in urban Queensland for any reason, 24% had a history of chronic cough in the previous 12 months, and at 12‐month follow‐up 26% had a further episode of chronic wet cough.15 Owing to multiple factors, chronic wet cough in First Nations children is often incorrectly considered a normal feature by both families and doctors.16,17 First Nations Australians who have been symptomatic since childhood are more likely to have considerably poorer clinical outcomes in adulthood than those who had onset symptoms in adulthood.18 Box 4 lists potential strategies in combatting chronic wet cough in First Nations patients.

Chronic cough: initial assessment of both children and adults

In both adults and children, estimating duration of cough is critical in assessment.3,22 A chronic cough is defined as a daily cough for > 4 weeks in children,3 and > 8 weeks in adults (Box 5).22 The initial assessment for chronic cough relies on history and examination to identify any red flags — indicators that may signal an underlying disease or systemic exposure (Box 6). Probability‐based algorithms are an important clinical decision tool and are presented for both children (Box 1) and adults (Box 2) separately. Initial assessment should always include a chest x‐ray and spirometry (age, > 6 years).2,3,22 Although a primary diagnosis may be made, it should be remembered that many common conditions co‐exist.

An assessment of risk factors and modification of such exposures is essential to the optimal management of chronic cough (Box 7). These risk factors are mostly common to both children and adults.

Diagnosis and management in children

In children, “specific cough” refers to a cough that occurs with a condition known to be associated with or cause a chronic cough. Identification of the conditions associated with chronic cough forms the basis of specific treatment and investigation. These conditions can usually be identified by cough characteristics and reviewing red flags (Box 6), a probability‐based diagnostic approach (Box 8), and consideration of important conditions not to be missed (Box 9). This approach has been validated in children.3

There is high quality evidence that using children‐specific cough management algorithms improves clinical outcomes, as shown in a systematic review that focused on chronic cough managed by specialists.26 This approach was supported by a randomised controlled trial (RCT) applying the cough management algorithm in community‐based children.12 Box 1 shows the paediatric algorithm, adapted from international ones.3,27,28

Causes of paediatric specific cough

Protracted bacterial bronchitis. This condition is considered in children with a chronic wet cough in the absence of other specific cough diagnoses or red flags.24 Chest x‐ray and spirometry are usually normal. Two to four weeks of antibiotic treatment (typically amoxicillin–clavulanate if no history of allergy) should lead to complete cough resolution29,30 [GRADE: Strong]. The diagnosis can only be definitive when patients become asymptomatic with treatment.24,31 A significant proportion of children with protracted bacterial bronchitis have ongoing symptoms at 5‐year follow‐up, including bronchiectasis in 9.6%; these children therefore require careful follow‐up and specialist referral if episodes recur more than three times per year or treatment fails (Box 1).32

Asthma. Asthma may cause a cough that is episodic and associated with other features such as expiratory wheeze and/or exertional dyspnoea. The diagnosis and management of asthma should be undertaken in accordance with paediatric asthma management guidelines. Treatment is expected to reduce symptoms within 2–4 weeks [GRADE: Strong]. In children, chronic cough in the absence of other symptoms/signs is seldom due to asthma, and inhaled corticosteroids are not indicated unless there are specific features to suggest asthma. When used, the trial period should be of a defined duration (eg, one month) to confirm or refute the provisional diagnosis.27

Allergic rhinitis. The evidence that postnasal drip is a significant cause of cough in children is not fully established, and when present, likely reflects co‐existing upper airway disease. Some paediatric studies reported upper airways cough syndrome as the aetiology of chronic cough,33 but we did not find high quality RCTs on therapies for upper airway disorders in children with cough, and in children, antihistamines have not been shown to be efficacious for the treatment of chronic cough.3 Allergic rhinitis can be diagnosed by symptoms of nasal itching, nasal blockage, or nasal discharge. Management should follow current guidelines [GRADE: Weak].34

Chronic rhinosinusitis. Chronic cough may occur concurrently in children with chronic rhinosinusitis.25 However, any association between rhinosinusitis and cough does not necessarily indicate causality. Notably, the bacterial pathogens associated with chronic rhinosinusitis are the same as those of protracted bacterial bronchitis, hence treatment recommendations for prolonged antibiotics (~ 2–4 weeks of amoxicillin–clavulanate) are similar.24,35 While there are currently insufficient data, this raises the question of whether the chronic wet cough in children with chronic rhinosinusitis is related to protracted bacterial bronchitis [GRADE: Weak].

Obstructive sleep apnoea. Obstructive sleep apnoea (OSA) is suggested by a history of snoring associated with witnessed apnoeas, sleep disturbance or sweating at night, excessive daytime sleepiness, failure to thrive (in infants), obesity, large tonsils, or nasal blockage. The association between cough and OSA is very weak.36 Hence, in children with OSA and cough, the OSA and cough should be evaluated and treated independently [GRADE: Weak].

Gastro‐oesophageal reflux disease. In children, gastro‐oesophageal reflux disease (GORD) is not commonly identified as a cause of chronic cough.25 There is little current convincing evidence that GORD is a common cause of isolated chronic cough (ie, without gastrointestinal‐related GORD symptoms) and proving causality is difficult.37 Thus, in line with international guidelines,3,33,38 CICADA recommends against empirical treatment for GORD in children with chronic cough and against fundoplication for the treatment of isolated cough in children (Box 10). When symptoms of GORD are present, paediatric GORD guidelines42 should be followed.

Tic and somatic cough syndrome. Tic (habit cough) and somatic cough syndrome (psychogenic cough) are characterised by a continuous, excessive dry barking/honking cough in a child with no red flags in their history or examination. The key indicator is that cough is absent in sleep. Treatment involves suggestion therapy without further investigation [GRADE: Weak].43,44

Non‐specific cough in children

Non‐specific cough is chronic dry cough without any cough pointers or cough‐associated diagnoses, and normal chest x‐ray and spirometry. Most children with non‐specific cough undergo spontaneous resolution or improvement,25 but they need to be reviewed to ensure that no new cough pointers emerge. The management of non‐specific cough adopts the approach of counsel, watch, wait and review [GRADE: Strong], and addresses parental stress and concerns [GRADE: Strong]. At each review, look out for specific pointers (Box 1). CICADA recommends against use of narcotic cough suppressants45 in children [GRADE: Strong].

Diagnosis and management in adults

The assessment of chronic cough in adults includes a history2,22 to define the duration and characteristics of the cough (sputum production, cough hypersensitivity, triggers), to elicit any red flags that suggest underlying disease (Box 6, Box 11)2,46 We recommend a chest x‐ray and spirometry followed by use of a probability‐based algorithm (Box 2) to identify whether these triggers are present and then to manage them to reduce chronic cough (Box 10, Box 12).

Causes of adult chronic cough

Asthma/eosinophilic bronchitis/cough variant asthma. Eosinophilic airway inflammation is found in 30–50% of adults with chronic cough47,48,49 and may reflect asthma, cough variant asthma, and eosinophilic bronchitis. Asthma is diagnosed in 24–32% of adults with chronic cough,48 and is associated with episodic chest tightness, wheeze and dyspnoea.41 Asthma diagnosis relies upon the presence of variable airflow obstruction (as measured by spirometry, peak flow monitoring) or bronchial hyperresponsiveness.39,41,50 Cough variant asthma, a subtype of asthma, is less common and presents solely with cough (without dyspnoea or wheeze), normal spirometry, and a positive bronchial provocation challenge.51 As asthma is commonly associated with chronic cough,19 we recommend spirometry, including post bronchodilator, be considered in the initial assessment of all patients with chronic cough. Eosinophilic bronchitis is characterised by an increase in lower airway eosinophils, normal spirometry, and negative bronchial provocation challenge.48,49 Fractional exhaled nitric oxide (FeNO) has been proposed as a surrogate marker of eosinophilic airway inflammation.2,52 FeNO has good diagnostic accuracy in predicting cough variant asthma, but was less sensitive in predicting eosinophilic bronchitis.53 Treatment of asthma, according to current management guidelines, has been shown to improve chronic cough [GRADE: Strong].

Chronic bronchitis/chronic obstructive pulmonary disease/bronchiectasis. In adults, chronic bronchitis is defined by recurring chronic cough with sputum production54 and has been described with and without chronic obstructive pulmonary disease, bronchiectasis, or a smoking history.55,56 Chronic bronchitis associated with chronic obstructive pulmonary disease and asthma is linked to more frequent exacerbations and worse outcomes.57 It is recommended to treat these underlying disorders [GRADE: Strong]. Non‐smoking adults with chronic bronchitis without airflow obstruction should be investigated for underlying lung disease such as bronchiectasis. Treatments trialled have included mucolytics and/or macrolide antibiotics, but the evidence for their use is scarce [GRADE: Weak].

Interstitial lung disease. Chronic cough that has been reported in up to 80% of people with interstitial lung disease58 is often severe, leads to a significantly impaired quality of life, and is associated with worse clinical outcomes.59

Laryngeal hypersensitivity/intermittent laryngeal obstruction/vocal cord dysfunction. Several well defined clinical syndromes comprise laryngeal dysfunction and often have overlapping symptoms.60 They can also be associated with intermittent laryngeal obstruction, which describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. Intermittent laryngeal obstruction is an important cause of chronic cough and dyspnoea and can mimic asthma.61 Speech pathology management including education, vocal hygiene training, breathing techniques, and psycho‐educational counselling are effective in reducing symptoms [GRADE: Strong].

Gastro‐oesophageal reflux disease/airway reflux. The prevalence of chronic cough associated with GORD in adults varies depending on the definition. When this requires the demonstration of acid reflux the prevalence is low;62 however, definitions based on symptoms or oesophageal dysmotility are more frequently associated with chronic cough. A systematic review identified nine RCTs that treated patients with acid suppression and no symptomatic GORD. Only two trials reported a reduction in cough frequency or severity, limited to those with abnormal 24‐hour pH monitoring.63 CICADA recommends against acid suppressive therapy without a history of reflux, or evidence of reflux on objective testing [GRADE: Strong].40

Chronic rhinosinusitis. Chronic rhinosinusitis (allergic or non‐allergic) is found in 12% of people from the United Kingdom presenting with chronic cough,64,65 and treatment follows current evidence‐based guidelines.39 Intranasal corticosteroids are the first line therapy, although evidence they improve chronic cough is weak [GRADE: Weak]. A systematic review of antihistamines66 (ten placebo‐controlled trials in chronic rhinitis, asthma or cough associated with allergy) found treatment led to improved cough symptom scores, although the effect appeared greatest in those with allergy [GRADE: Weak].

Cough hypersensitivity syndrome. Cough hypersensitivity syndrome describes excessive coughing triggered by low levels of thermal, mechanical or chemical stimuli, and can be the result of multiple triggers (Box 11).2,46 Where cough persists beyond management of triggers, it is called unexplained chronic cough.

Adult unexplained chronic cough

Where cough persists despite optimal treatment of diagnosed conditions, it is termed refractory chronic cough (RCC). If no identifiable cause for the cough can be determined, it is termed unexplained chronic cough (UCC), estimated to occur in 10% of adult chronic cough,2,67 and is clinically important.64 We recommend referral for all adults with RCC or UCC to a specialist respiratory clinic.

Therapies for RCC/UCC in adults. Specialists use several options to treat RCC and UCC, including speech therapy and/or antitussive therapies. Two RCTs of speech therapy in adults with RCC or UCC found benefits.68,69 We recommend speech pathology for RCC and UCC [GRADE: Strong], following assessment by respiratory/otolaryngology clinics.

The evidence‐base for antitussive therapies in RCC/UCC is not strong, and a trial of treatment under the supervision of specialist is recommended. The trial should be of sufficient duration to establish efficacy using objective measures of cough severity.70

Inhaled corticosteroids. Inhaled corticosteroids (ICSs) are often trialled in RCC/UCC empirically. A response to treatment should be seen within 4 weeks, and if not evident, ICSs should be ceased. Every effort should be made to diagnose asthma and demonstrate variable airflow obstruction, as this predicts response to ICSs.2 In RCC/UCC, the evidence for empirical ICS use is weak, and there are greater odds of cough improvement with an elevated FeNO (> 50 ppB) [GRADE: Weak].71

The use of leukotriene receptor antagonists is limited to small open label trials.72 The evidence for their use is weak and may be independent of FeNO [GRADE: Weak].

Antibiotics. A small trial of azithromycin in RCC/UCC found no improvement in cough scores, except for a subgroup with asthma where a significant improvement was seen.73 There is no evidence for other antibiotic regimens. We recommend against the use of empirical antibiotic trials [GRADE: Weak].

Neuromodulators. Two systematic reviews investigating neuromodulators including amitriptyline, gabapentin, pregabalin and baclofen consistently found improvements in cough symptoms and quality of life in RCC/UCC.74,75 A trial of neuromodulators could be considered in RCC/UCC [GRADE: Weak].

Opioids. There are short term trials76 showing that low dose morphine reduces RCC/UCC; however, CICADA recommends against its use in chronic cough given concerns and limitations regarding long term use of opioids [GRADE: Weak].

Specific antitussive therapies. Although the detailed neurophysiology of cough is beyond the scope of this statement, changes in the activity and sensitivity of peripheral and central cough neural circuits are critical to chronic cough pathology and a targetable mechanism. There is emerging evidence for the use of specific antitussive agents for RCC/UCC, but none are yet approved for use in Australia.

Conclusion

Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. We have presented an updated Australian position statement on cough management in the clinical consultation.

The main recommendations are:

Assessment of children and adults requires a focused history of the chronic cough to elicit any red flag cough pointers that may indicate an underlying disease.
Further assessment with examination should include a chest x‐ray and spirometry (age, > 6 years).
Separate paediatric and adult diagnostic management algorithms should be followed.
Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns.
Aboriginal and Torres Strait Islander adults and children should be considered high risk groups.

Full details of the position statement update, complete reference list, and chronic cough health professional and consumer resources developed in conjunction are available from Lung Foundation Australia at https://lungfoundation.com.au/resources/cicada‐full‐position‐statement.

Box 1 – Algorithm for diagnosis and assessment of a child with chronic cough

PBB = protracted bacterial bronchitis

Box 2 – Algorithm for diagnosis and assessment of an adult with chronic cough

ACE = angiotensin‐converting enzyme; COPD = chronic obstructive pulmonary disease; CT = computed tomography; ENT = ear, nose and throat; ICS = inhaled corticosteroids; FeNO = fractional exhaled nitric oxide; GORD = gastro‐oesophageal reflux disease; ppb = parts per billion; RAST = radioallergosorbent test; SPT = skin prick test.

Box 3 – Guideline development process

From Jan 2021 to December 2022, members of the CICADA committee regularly convened (email, face‐to‐face, virtual meetings) to undertake an extensive literature review and discuss recommendations.
The committee included several working groups (children, adult, epidemiology and prevention, overall approach) who undertook systematic searches for relevant literature published since 2010 (the previous CICADA update),4 including but not limited to “all RCTs, systematic reviews, guidelines, position statements in any setting”.
Databases searched included OVID MEDLINE, PubMed, the Cochrane Library, and Embase. Search results were then screened (total 6395 abstracts); a total of 277 new studies were included in this statement. The search strategies, PRISMA diagrams, full reference list of included evidence, and complete guideline document are available on the Australian Lung Foundation website at https://lungfoundation.com.au/resources/cicada‐full‐position‐statement/.
The recommendations use the principles of evidence‐based medicine5 and the GRADE approach to guide recommendations to inform the strength of the evidence: strong, weak, or no specific recommendation.6
The implications of strong recommendation are:
1. ‣ for patients — most people in your situation would want the recommended course of action and only a small proportion would not; suggest request discussion if the intervention is not offered
2. ‣ for clinicians — most patients should receive this recommended course of action
3. ‣ for policy makers — the recommendation can be adopted as a policy in most situations.
The implications of a weak recommendation are:
1. ‣ for patients — some people in your situation would want the recommended course of action, but many would not
2. ‣ for clinicians — you should recognise that different choices will be appropriate for different patients and that you must help each patient to arrive at a management decision consistent with their values and preferences
3. ‣ for policy makers — policy making will require substantial debate.

Box 4 – Specific recommendations for addressing chronic cough in First Nations people

Recommendations

Level of evidence*

Strength of recommendation^†

Address environmental factors: air quality (airborne particulate matter), cigarette smoke exposure (patient, parental, household)19

Good

Strong

Provide culturally secure health information to facilitate detection of chronic wet cough: accurate history taking in First Nations settings, provision of appropriate health information in a culturally secure way, community engagement at a local level20

Satisfactory

Strong

Implement strategies in health systems that include targeted training of clinicians; implementation programs that include targeted training of clinicians, health system changes and the provision of culturally secure health information tools have been shown to improve physician assessment of chronic cough and appropriate antibiotic prescription20

Satisfactory

Strong

Utilise chronic cough management algorithms; randomised controlled trials including First Nations children have shown the effectiveness of management algorithms for chronic cough, usual care12,21

Excellent

Strong

* NHMRC additional levels of evidence and grades for recommendations for developers of guidelines.5 † The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the strength of recommendations.6

Box 5 – Definitions of cough3,22

Cough: protective respiratory behaviour of forced expulsion of air against a closed glottis
Acute cough: cough lasting up to 2 weeks
Protracted acute cough:
1. ‣ in children — cough lasting 2 to 4 weeks
2. ‣ in adults — cough lasting 2 to 8 weeks
Chronic cough:
1. ‣ in children — cough lasting more than 4 weeks
2. ‣ in adults — cough lasting more than 8 weeks

Box 6 – Red flags and cough pointers (indicators of serious pathology)

Children 23

Dyspnoea (at rest or exertional)
Recurrent episodes of chronic or wet or productive cough
Recurrent pneumonia
Chest pain
Haemoptysis
Systemic symptoms: fever, weight loss, growth failure
Neurodevelopmental abnormality
Feeding difficulties (including choking/vomiting)
Stridor and other respiratory noises
Abnormal clinical respiratory examination (eg, crackles, digital clubbing)
Abnormal systemic examination (eg, growth failure)
Abnormal chest x‐ray
Abnormal lung function
Co‐existing chronic diseases (eg, immunodeficiency, syndromes)

Adults

Haemoptysis
Smoking/vaping (especially new/altered cough, cough with voice disturbance)
Prominent dyspnoea (especially at rest or at night)
Chronic productive cough with substantial sputum production
Hoarseness
Recurrent pneumonia
Systemic symptoms: fever, weight loss
Swallowing difficulties (including choking/vomiting)
Abnormal clinical respiratory examination (eg, crackles, wheeze, digital clubbing)
Abnormal chest radiograph

Box 7 – Preventive strategies for chronic cough

Immunisations: pneumococcus, Haemophilus influenzae, Bordetella pertussis, influenza
Avoidance of airway pollutants, irritants and triggers:
1. ‣ cigarette smoke, wood‐fire smoke, e‐cigarettes
2. ‣ fumes, strong odours, subfreezing air
3. ‣ for those susceptible, animals, pollens, and other allergens
Health education:
1. ‣ early clinical review and adequate treatment of a chronic wet cough including post‐acute respiratory infection (> 4 weeks in children, > 8 weeks in adults)
2. ‣ workplace education about hazard minimisation for workers in high risk occupations

Box 8 – Probability‐based diagnosis of chronic cough in children

If the examination, chest x‐ray and spirometry are normal, the most common diagnoses and exposures associated with chronic cough in children are:

Diagnoses:
1. ‣ Protracted bacterial bronchitis (if wet/productive cough and no other systemic symptoms or signs)24
2. ‣ Asthma (if other respiratory symptoms are present)25
Exposures:21
1. ‣ Respiratory infection (post‐infectious cough, including pertussis)
2. ‣ Tobacco smoke or e‐cigarettes/vaping and other pollutants (active, environmental) can exacerbate chronic cough but are rarely the cause

Box 9 – Significant conditions in children with chronic cough3,25

Condition

Typical symptoms

Diagnoses with specific removable causes or usually good treatment response

Protracted bacterial bronchitis

Wet/productive cough and no other systemic symptoms or signs24

Asthma

Recurrent wheeze and/or dyspnoea responsive to β₂ agonists

Tic (habit cough) and somatic cough syndrome (psychogenic cough)

Continuous, excessive dry cough with no sign of physical disease; stops when asleep or distracted

Significant conditions not to be missed

Congenital airway abnormalities

Symptoms commencing in infancy/early childhood

Recurrent aspiration

Cough or choking with feeds

Foreign body inhalation

Symptoms commenced after choking episode

Chronic infection

Tuberculosis

Focal signs, weight loss lymphadenopathy, contact history

Lung abscess

Fever and local signs

Pertussis

Dry cough, contact history; paroxysms in unvaccinated children

Bronchiectasis/chronic suppurative lung disease/cystic fibrosis

Wet cough not responding to 4 weeks of antibiotics or recurring

Chronic atelectasis

Focal signs on auscultation

Interstitial lung disease

Diffuse inspiratory crepitations growth failure with or without hypoxia

Box 10 – Strength of recommendations for the efficacy of treatment of cough in association with the conditions

Recommendations

Level of evidence*

Strength of recommendation^†

Children

Cessation of parental smoking to reduce cough

Good

Strong

Cough with allergic rhinitis

Treatment according to current rhinitis management guidelines involving topical nasal corticosteroid, antihistamines, and allergen management

Poor

Weak

Cough with obstructive sleep apnoea

Tonsillectomy and adenoidectomy

Poor

Weak

Cough with asthma

Treatment according to current asthma management guidelines involving education and self‐management, inhaled bronchodilators, and inhaled corticosteroids; if empirical treatment is used, review in 2–4 weeks

Good

Strong

Cough with protracted bacterial bronchitis

Medium term (2–4 weeks) antibiotics for protracted bacterial bronchitis

Excellent

Strong

Cough with GORD

Treatment(s) for GORD should not be used when there are no gastro‐intestinal clinical features of GORD; paediatric GORD guidelines should be used to guide treatment and investigations

Good

Weak

Treatment with laparoscopic fundoplication

Poor

Strong recommendation against

Non‐specific or refractory cough

Address patient/parental stress and concerns

Poor

Strong

Address exacerbating factors, such as tobacco smoke exposure

Good

Strong

Minimise use of medications other than demulcents (eg, honey) if no contraindications (young age) exist

Good

Strong

Adopt counsel, watch, wait and review approach

Excellent

Strong

Empirical trial of inhaled corticosteroid therapy

Poor

No recommendation

Empirical trial of proton pump inhibitors

Good

Strong recommendation against

Speech pathology techniques designed to relieve glottal constriction during inspiration and to recognise and alter response to precipitants

Poor

No recommendation

Antitussive therapy with narcotic

Good

Strong recommendation against

Adults

Cough with allergic rhinitis

Treatment according to current rhinitis management guidelines39 involving nasal corticosteroid spray, nasal antihistamine spray, combination corticosteroid/antihistamine nasal spray

Good

Weak

Cough with chronic rhinosinusitis

Treatment according to current chronic sinusitis management guidelines39 involving nasal corticosteroid spray, large volume saline irrigation, long term antibiotic therapy (macrolide, 3 months)

Poor

Weak

Cough with laryngeal hypersensitivity

Treatment with speech pathology management

Good

Strong

Cough with vocal cord dysfunction/intermittent laryngeal obstruction

Treatment with speech pathology management

Good

Strong

Cough with GORD/dysmotility

Treatment(s) for GORD in adults with cough alone and no other symptoms of GORD with PPI therapy; when other symptoms of GORD occur, use appropriate clinical guidelines40

Good

Strong recommendation against use of PPI for cough alone

Cough with asthma

Treatment according to current asthma management guidelines41 involving education, inhaled bronchodilators, inhaled corticosteroids

Excellent

Strong

Leukotriene receptor antagonists, alone or with inhaled corticosteroids

Good

Weak

Cough with eosinophilic bronchitis

Treatment with inhaled corticosteroids

Satisfactory

Strong

Leukotriene receptor antagonists, alone or with inhaled corticosteroids

Satisfactory

Weak

Cough with chronic bronchitis without airflow obstruction

Mucolytic therapy and/or macrolide antibiotic therapy

Poor

Weak

Cough with ILD

Treatment according to current ILD guidelines

Poor

Weak

Cough with COPD

Treatment according to current COPD management guidelines involving education and self‐management, smoking cessation, pulmonary rehabilitation and treatment of exacerbations

Excellent

Strong

Addition of combination inhaled long‐acting bronchodilators and corticosteroids may reduce cough severity

Good

Weak

Cough with bronchiectasis

Treatment according to current bronchiectasis management guidelines involving treatment of exacerbations with 14 days antibiotics, regular airway clearance and pulmonary rehabilitation

Good

Weak

Unexplained chronic cough

An empirical treatment trial supervised by a specialist cough clinic using validated, objective measures of cough severity (cough severity scales, the cough severity diary, quality‐of‐life measures [Leicester cough questionnaire, cough specific quality of life questionnaire], objective cough recording devices and cough reflex sensitivity challenges)

Satisfactory

Weak

Cessation of smoking, nicotine containing cigarettes or e‐cigarettes

Excellent

Strong

Identify and minimise environmental/occupational exposures

Satisfactory

Weak

Cessation of angiotensin‐converting enzyme inhibitors

Satisfactory

Strong

Speech and language therapy

Excellent

Strong

Inhaled corticosteroids or leukotriene antagonist empirical treatment trial

Poor

Weak

Macrolide antibiotics

Satisfactory

Weak recommendation against

Acid suppressive therapy, proton pump inhibitors, or H2 antagonist empirical treatment trial

Excellent

Strong recommendation against

Neuromodulators (amitriptyline, gabapentin, pregabalin) treatment trial

Satisfactory

Weak

Opioids empirical treatment trial

Satisfactory

Weak recommendation against

COPD = chronic obstructive pulmonary disease; GORD = gastro‐oesophageal reflux disease; H2 = histamine type 2; ILD = interstitial lung disease; PPI = proton pump inhibitor. * NHMRC additional levels of evidence and grades for recommendations for developers of guidelines.5 † GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.6

Box 11 – Conditions associated with chronic cough in adults

ACE = angiotensin‐converting enzyme; COPD = chronic obstructive pulmonary disease; GORD = gastro‐oesophageal reflux disease; ILD = interstitial lung disease; ILO = intermittent laryngeal obstruction. Reproduced with permission from Lung Foundation Australia.

Box 12 – Conditions associated with chronic cough in adults

Condition

Key features

Investigations

Chronic rhinitis

Nasal obstruction (variable or persistent), loss of smell, nasal discharge

RAST/SPT
Anterior rhinoscopy

Chronic sinusitis

Nasal obstruction, and at least one other of nasal discharge, postnasal drip, reduction/loss of sense of smell, facial pain

RAST/SPT
CT sinuses

Laryngeal hypersensitivity

Hypersensitive cough reflex, allotussia

Laryngeal Hypersensitivity Questionnaire

Vocal cord dysfunction/inspiratory laryngeal obstruction

Inspiratory dyspnoea
Throat tightness, dysphonia, sensation of choking/suffocation

Functional laryngoscopy
Laryngeal CT
Flattened inspiratory loop of flow volume curve

GORD/dysmotility

Heartburn, reflux symptoms
Cough associated with meals

Oesophageal manometry
pH‐metry (resistant cases)

Post infectious

Post acute respiratory illness

Bordetella pertussis serology
CT chest

Asthma/cough variant asthma/eosinophilic bronchitis without asthma

Wheeze, dyspnoea
Cough as the only symptom

Spirometry (bronchodilator reversibility)
Elevated FeNO
Peak flow variability
Bronchial provocation challenge
Reversible airflow limitation as for asthma, FeNO, may require bronchial provocation challenge to rule out
No evidence of variable airflow obstruction
Elevated FeNO

Chronic non‐eosinophilic bronchitis

Sputum production without airflow obstruction

Spirometry: pre/post bronchodilator to exclude asthma and COPD
Consider bronchiectasis and need for HRCT chest

Interstitial lung disease

Presence of dyspnoea

HRCT chest, history (exposures, serology)

COPD

Exertional dyspnoea, sputum production, history of smoking/exposure to noxious agents

Spirometry (post bronchodilator FEV₁/FVC < 0.7)

Bronchiectasis

Sputum production, chronic bronchial infection

HRCT chest

Congestive cardiac failure

Dyspnoea, peripheral oedema, crackles +/‐wheeze on auscultation

ECG, CXR, BNP or
NT‐BNP Echocardiography

Lung cancer

Haemoptysis, dyspnoea, chest pain, history of smoking, constitutional symptoms

CT scan of the chest, bronchoscopy, PET scan

BNP = B‐type natriuretic peptide; COPD = chronic obstructive pulmonary disease; CT = computed tomography; CXR = chest x‐ray; ECG = electrocardiogram; FeNO = fractional exhaled nitric oxide; FEV₁ = forced expiratory volume; FVC = forced vital capacity; GORD = gastro‐oesophageal reflux disease; HRCT = high resolution computed tomography; NT‐BNP = N‐terminal pro hormone BNP; PET = positron emission tomography; RAST = radioallergosorbent test; SPT = skin prick test.

Provenance: Not commissioned; externally peer reviewed.

View this article on Wiley Online Library

Julie M Marchant¹^,²
Anne B Chang¹^,²^,³
Emma Kennedy⁴
David King⁵
Jennifer L Perret⁶
Andre Schultz⁷^,⁸
Maree R Toombs⁹
Lesley Versteegh³
Shyamali C Dharmage⁶
Rebecca Dingle¹⁰
Naomi Fitzerlakey¹⁰
Johnson George¹¹
Anne Holland¹²^,¹³^,¹⁴
Debbie Rigby⁵^,¹⁵
Jennifer Mann¹⁴^,¹⁶
Stuart Mazzone¹⁷
Mearon O'Brien¹⁰
Kerry‐Ann O'Grady¹
Helen L Petsky¹⁸
Jonathan Pham¹⁹
Sheree MS Smith²⁰
Danielle F Wurzel²¹
Anne E Vertigan²²^,²³
Peter Wark²²^,²³

1 Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, QLD
2 Queensland Children's Hospital, Brisbane, QLD
3 Menzies School of Health Research, Darwin, NT
4 Rural and Remote Health, Flinders University, Darwin, NT
5 University of Queensland, Brisbane, QLD
6 Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC
7 Wal‐yan Respiratory Research Centre, Perth, WA
8 Perth Children's Hospital, Perth, WA
9 University of Sydney, Sydney, NSW
10 Lung Foundation Australia, Brisbane, QLD
11 Centre for Medicine Use and Safety, Monash University, Melbourne, VIC
12 Alfred Health, Melbourne, VIC
13 Monash University, Melbourne, VIC
14 Institute for Breathing and Sleep, University of Melbourne, Melbourne, VIC
15 Queensland University of Technology, Brisbane, QLD
16 Austin Health, Melbourne, VIC
17 University of Melbourne, Melbourne, VIC
18 Griffith University, Brisbane, QLD
19 Alfred Health, Melbourne, VIC
20 Western Sydney University, Sydney, NSW
21 Royal Children's Hospital, Melbourne, VIC
22 Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW
23 John Hunter Hospital, Newcastle, NSW

Correspondence: jm.marchant@qut.edu.au

Open access:

Open access publishing facilitated by Queensland University of Technology, as part of the Wiley ‐ Queensland University of Technology agreement via the Council of Australian University Librarians.

Acknowledgements:

We thank Lung Foundation Australia and the Thoracic Society of Australia and New Zealand for their support in the preparation of these guidelines.

Competing interests:

The authors received no specific funding for this work. Julie Marchant is supported by the Lung Foundation Australia Hope Research Fund Andrew Harrison Fellowship in Bronchiectasis Research 2021 and receives personal fees from being an author of two UpToDate chapters, outside of the submitted work. Anne Chang reports multiple grants from the National Health and Medical Research Council (NHMRC) during the conduct of this work; is an independent data monitoring committee member for an unlicensed vaccine (GSK) and an unlicensed monoclonal antibody (AstraZeneca); is an advisory member on the study design for an unlicensed molecule for chronic cough (Merck); and has received personal fees from being an author of two UpToDate chapters, outside the submitted work. Andre Schultz receives salary support from a Medical Research Future Fund Investigator Grant (APP1193796). Danielle Wurzel has received research grants from the NHMRC and GSK, and honoraria from Merck and MSD. Stuart Mazzone has received honoraria from Merck, NeRRe Therapeutics, Reckitt Benckiser and Bellus Health for consultancy on their antitussive programs, and antitussive‐related grant support from Merck, Bellus Health and Reckitt Benckiser, as well as multiple grants from the NHMRC and the Australian Research Council. Shyamali Dharmage has received multiple grants from the NHMRC and the Australian Research Council, including the NHMRC Investigator Grant (APP1193993) that currently supports her. Additionally, Shyamali Dharmage and Jennifer Perret have received independent investigator‐initiated grants from AstraZeneca and GSK for unrelated research. Jennifer Perret is supported by an NHMRC Early Career Fellowship (APP1159090). Johnson George has received honoraria through consultations for AstraZeneca, GSK and Pfizer which have been paid to his employer, and has held research grants from Boehringer Ingelheim, GSK and Pfizer through investigator‐initiated research schemes. All other authors have no conflicts of interest to declare in relation to this work.

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