National Guide

Chapter 14 | Respiratory health

Bronchiectasis and chronic suppurative lung disease







National Guide to preventive healthcare for Aboriginal and <br/>Torres Strait Islander people
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      3. Bronchiectasis and chronic suppurative lung disease

Respiratory health | Bronchiectasis and chronic suppurative lung disease

Prof Anne Chang, Dr Pamela Laird, Ms Lesley A Versteegh   

Key messages

  • Bronchiectasis is a significant health issue for Aboriginal and Torres Strait Islander children and adults, with high prevalence and poorer outcomes compared with non-Indigenous Australians.
  • Bronchiectasis was historically defined as irreversible airway dilatation based on high-resolution computed tomography (HRCT) chest scans. Bronchiectasis is now defined as a clinical syndrome with radiological evidence of abnormally dilated airways.1–3
  • Bronchiectasis can be prevented by prevention and comprehensive treatment of severe and recurrent respiratory infection in children and adults.
  • Other chronic respiratory diseases and comorbidities overlap with bronchiectasis and these should be diagnosed and treated appropriately.2,3
  • Early diagnosis and effective management support health and wellbeing and reduce exacerbations, hospitalisations and death. In children, effective management can reverse radiological bronchiectasis.1
  • Effective management includes effective education, using age-appropriate airway clearance techniques, regular clinical review, monitoring of lower airway bacteria, rehabilitation (when appropriate) and having a bronchiectasis management plan with good communication between primary, secondary and tertiary care.
Type of preventive activity - Immunisation
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
All children and adults, including pregnant women Ensure timely immunisation is provided, including COVID-19, pneumococcal and annual influenza vaccine As per the Australian immunisation handbook4 and state and territory schedules Strong National guideline4 Timely vaccination as per guidelines is required to optimise effectiveness in preventing acute respiratory illnesses (ARIs)
Type of preventive activity - Screening
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
People with pneumonia and acute lower respiratory infections (ALRIs), particularly following hospitalisation Review the patient after the ALRI episode to determine presence of respiratory symptoms/signs

If wet or productive coughA is present:
  • consider the diagnosis of bronchiectasis/chronic suppurative lung disease (CSLD)B
  • Recommence antibiotics and undertake investigations as per management guidelines (refer to Useful resources)
  • Assess for need to refer to a respiratory specialist (Box 1)
 Three to four weeks after the episode, then every two weeks until symptoms resolve or referral to a respiratory specialist is made Strong Single studies5–7
Systematic review and guideline8–10		 The presence of cough at three to four weeks after discharge for an ALRI increased the odds of having bronchiectasis diagnosed by 13 months in Aboriginal children.7 There is high-level evidence that antibiotics are efficacious for chronic wet cough8,9

Being hospitalised for pneumonia is associated with future bronchiectasis.5,6 In addition, pneumonia in early childhood is a risk factor for reduced lung function11
People with recurrent ALRIs (in children, two or more episodes of hospitalised, chest-X-ray-proven pneumonia ever) and/or with persistent (more than four weeks) wet coughB Consider a diagnosis of bronchiectasis. Repeat a chest X-ray to ensure resolution of chest X-ray changes

Refer children to a specialist if there is persistent wet cough and/or abnormal  chest X-ray (Box 1)		 As clinically indicated Strong Guidelines and single studies5,7–10,12 Recurrent ALRIs are associated with bronchiectasis. 13 In addition, being hospitalised for pneumonia is associated with future bronchiectasis.5

Earlier diagnosis leading to earlier optimal treatment of bronchiectasis leads to better outcomes (eg reversibility of bronchiectasis1,2 and better lung function14). Pneumonia in early childhood is a risk factor for reduced lung function11
People with a history of tuberculosis Assess for chronic lung disease symptomsC and undertake spirometry As clinically indicated Strong Single studies15,16 People with tuberculosis are at increased risk of chronic lung disease, including bronchiectasis
Adults with chronic obstructive pulmonary disease (COPD) Undertake spirometry

Assess for bronchiectasis symptoms and consider referral to a specialist if:
  • there is a history of daily sputum production
  • sputum has persistent infection, especially with Pseudomonas aeruginosa
  • there are increasing exacerbations
  • there is lung function decline
  • there are two or more exacerbations per year
(Refer to Chapter 14: Respiratory health, Chronic obstructive pulmonary disease).		 As clinically indicated Strong National guideline12 Other chronic respiratory diseases and comorbidities overlap with bronchiectasis, and these should be diagnosed and treated appropriately

Guidelines recommend investigation for bronchiectasis in patients with COPD who have two or more exacerbations annually and a previous positive sputum culture for P. aeruginosa while clinically stable3
All children and adults Ask about the presence of chronic wet or productive cough (more than four weeks in children17 and more than eight weeks in adults18) Opportunistically Conditional International position statement and guidelines2,12,19 Productive cough is the most common symptom of bronchiectasis2
Longer duration of chronic cough correlates with poorer lung function14,20 and worse radiological scores21

Recurrent (more than three episodes per year) protracted bacterial bronchitis is associated with future bronchiectasis22
Type of preventive activity - Behavioural
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
Pregnant and lactating women Promote and encourage breastfeeding During antenatal and postnatal care Strong Guideline and single study5,12 Breastfeeding protects against bronchiectasis5,12
All children and adults Promote adequate nutrition, including vitamin D
(See Chapter 2: Healthy living and health risks, Healthy eating)		 Opportunistically Good practice point Guideline and single study23,24 Healthy nutritional status is essential for optimal immune efficiency25
Vitamin D deficiency is associated with increased ARI in Aboriginal and Torres Strait Islander children23,26 and poorer clinical outcomes in adults with bronchiectasis24
People with CSLD or known bronchiectasis Monitor to assess cough severity, quality of life and exacerbating frequency and factors

Undertake regular review to prevent and manage complications and comorbidities (Box 2)

Refer if symptoms are deteriorating		 Three-monthly review
Six-monthly specialist review		 Good practice point National guidelines2,3,12,27 Optimal treatment reduces deterioration and, in children, can reverse bronchiectasis2
Infants at risk of exposure to tobacco smoke both in utero and in the postnatal period Advise and assist pregnant women to avoid smoking (refer to Chapter 5: Preconception and pregnancy care, Pregnancy care

Advise parents/carers who smoke about the harms of second-hand tobacco smoke and the need to avoid childhood exposure, particularly in confined spaces, such as homes and motor vehicles (refer to Chapter 2: Healthy living and health risks, Smoking)		 As clinically indicated Strong National guidelines2,3,12 Exposure to tobacco smoke is associated with lower birth weights, increased ARI28,29 and double the risk of being readmitted with a respiratory illness within 6 months of hospital discharge7

The harm from third-hand smoke (residual substances and chemicals from tobacco smoke on/absorbed by surfaces) are also increasingly appreciated30
Teenagers and adults who smoke or vape Advise and assist smoking cessation, including e-cigarettes and cannabis (refer to Chapter 2: Healthy living and health risks, Smoking) Opportunistically Strong National guidelines31,32 The harms of smoking are well established
People with CSLD or known bronchiectasis Consider maintenance antibiotics after discussion with the person’s specialist As per clinical practice guidelines2,3,33 Strong Meta-analysis and randomised controlled trials34,35 Exacerbations are associated with more rapid lung function decline. Regular macrolides halve the frequency of exacerbations2,3
People with CSLD or known bronchiectasis Asthma-type medications in those with airway eosinophilia As per clinical practice guidelines2,3,33 Good practice point International guidelines2,3,33 Asthma medications should not be routinely used in people with bronchiectasis. However, in the subset of people who have airway eosinophilia, asthma-type medications may be beneficial36
Type of preventive activity - Medications
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
People with CSLD or known bronchiectasis Consider maintenance antibiotics after discussion with the person’s specialist As per clinical practice guidelines2,3,33 Strong Meta-analysis and randomised controlled trials34,35 Exacerbations are associated with more rapid lung function decline. Regular macrolides halve the frequency of exacerbations2,3
People with CSLD or known bronchiectasis Asthma-type medications in those with airway eosinophilia As per clinical practice guidelines2,3,33 Good practice point International guidelines2,3,33 Asthma medications should not be routinely used in people with bronchiectasis. However, in the subset of people who have airway eosinophilia, asthma-type medications may be beneficial36
Type of preventive activity - Environmental 
Who/target population What When Strength of recommendation Key source(s) and reference(s) Rationale/key considerations informing recommendation
All children and adults Promote avoidance of airborne pollutants, including traffic emissions, biomass smoke and other settings with poor air quality Opportunistically Good practice point National guideline12 Environmental air pollutants37 exacerbate chronic respiratory disorders and constitute an additional risk factor for those with CSLD or bronchiectasis

Patients aged >65 years may be more susceptible to the adverse effects of air pollution38

Living near a major road has been associated with increased mortality in bronchiectasis37
Health services and practices in settings where environmental and living conditions have a strong contribution (environmental attribution) to communicable disease transmission and other conditions such as bronchiectasis and CSLD Know about diseases with a high environmental attribution

Develop a safe clinical relationship in order to  sensitively ask about housing and living conditions (inadequate housing facilities; access to affordable and reliable energy supply for refrigeration and air conditioning; access to health hardware, such as working plumbing for clean drinking water and washing facilities; access to hygiene; and sanitation supplies)

Know about local arrangements for environmental health referral
Offer an environmental health referral according to local arrangements, ensuring consent is obtained when a home visit is involved

Advocate with Aboriginal and Torres Strait Islander leaders for adequate housing, affordable and clean energy supply, facilities for washing and general living conditions

Provide community-based health promotion about environmentally attributable diseases

Check local guidelines		 Opportunistically, in response to any diagnosis or condition with an environmental attribution and as part of general healthcare Good practice point International and Aboriginal and Torres Strait Islander-specific narrative reviews39,40 Household crowding and the quality of housing and environments exacerbate conditions promoting communicable disease transmission, including COVID-19, Group A Streptococcus (Strep A) infections, otitis media, trachoma, tuberculosis and other respiratory tract infections
Aboriginal and Torres Strait Islander peoples have long recognized the links between human health, animal health and the environment. GPs can contribute to effective advocacy for adequate housing and living conditions

ACough is usually under-reported.41,42
BChildren do not usually produce sputum; hence the term ‘wet cough’ (rather than ‘productive cough’) is used.2
CBronchiectasis refers to symptoms of CSLD in the presence of HRCT chest scan findings of abnormal airway dilatation when clinically stable. CSLD is diagnosed when symptoms and/or signs of bronchiectasis are present without the availability of an HRCT to confirm bronchiectasis or, in children, without the HRCT features of bronchiectasis.12 These symptoms and/or signs are recurrent (ie more than three episodes) wet or productive cough, each lasting for more than four weeks, with or without other features (eg exertional dyspnoea, symptoms of airway hyper-responsiveness, recurrent chest infections, haemoptysis, growth failure, digital clubbing, hyperinflation or chest wall deformity).12
 

Box 1. In children, triggers for referral to a specialist include one or more of the following:1,12

  • Persistent wet cough not responding to four weeks of antibiotics
  • More than three episodes of chronic (more than four weeks) wet cough per year responding to antibiotics
  • A chest radiograph abnormality persisting more than six weeks after appropriate therapy
  • Recurrent pneumonia (two or more episodes of chest-X-ray-proven pneumonia)
 

Box 2. Regular review2,3

  • Regular review consists of at least an annual review in adults and every six months in children. A multidisciplinary team is recommended. The review includes assessment of:
  • Severity, which includes oximetry and spirometry
  • Sputum culture (when available) for routine bacterial and annual mycobacterial culture
  • Management of possible complications and comorbidities, particularly for gastroesophageal reflux disease/aspiration, reactive airway disease/asthma, COPD, otorhinolaryngeal disorders, urinary incontinence, mental health and dental disease; less commonly, patients require assessments for sleep-disordered breathing and cardiac complications
  • Adherence to therapies and knowledge of disease processes and treatments.
  • Use culturally appropriate resources and information to support patient and community knowledge about bronchiectasis.
  • Increase awareness of the importance of recognising and treating persistent wet or productive cough.
  • Encourage staff training to increase knowledge and skills in preventing, recognising and managing bronchiectasis.

Clinical guidelines

 

Clinical resources and training

 
 

Background

Definition

Bronchiectasis was historically defined as irreversible airway dilatation based on HRCT chest scans. Bronchiectasis is now defined as a clinical syndrome with radiological evidence of abnormally dilated airways.1–3 However, this radiological definition is problematic, particularly for Aboriginal and Torres Strait Islander people living in remote areas where access to computed tomography (CT) can be limited, and for very young children who would require a general anaesthetic to have a CT scan.12 In clinical guidelines that include recommendations specific to Aboriginal and Torres Strait Islander people,12 an additional term of ‘CSLD’ is used when symptoms and/or signs of bronchiectasis are present without available confirmation of HRCT features.12 In this document, bronchiectasis is used to refer to both bronchiectasis and CSLD. The clinical syndrome of bronchiectasis includes recurrent (more than three) episodes of wet or productive cough, each lasting for more than four weeks, with or without other features, including exertional dyspnoea, symptoms of airway hyper-responsiveness, recurrent lower respiratory tract infections (including pneumonia), haemoptysis, growth failure, digital clubbing, hyperinflation and chest wall deformity.1–3

Prevalence and outcomes

Although the incidence of bronchiectasis generally declined over the past century, in the past decade it has become increasingly recognised as an important contributor to chronic respiratory morbidity in Aboriginal and Torres Strait Islander people13,43 and in non-Indigenous Australian children and adults,44,45 as well as globally.20 In Aboriginal and Torres Strait Islander people, anecdotally bronchiectasis is common but there is a scarcity of confirmatory radiological data. In the Northern territory (NT), the incidence of bronchiectasis in Aboriginal and Torres Strait Islander infants (first year of life) is 1.18 per 1000 child years (95% confidence interval [CI] 0.60–2.16)46 and the prevalence is 1 in every 68 children aged <15 years.47 In a whole-population paediatric (age <18 years) survey in the Kimberley, the prevalence of CSLD was 3.3% and that of bronchiectasis was 1.3%.48 Overall, Australian hospitalisation rates for bronchiectasis as a principal diagnosis between 2007–08 and 2016–17 increased steadily (from 20 to 28 per 100,000 population, respectively), whereas the rate in Central Australia was 103 per 10,000 population in 2000–06.49 In Queensland, the hospitalisation rate for bronchiectasis in Aboriginal and Torres Strait Islander peoples was approximately 2.7-fold that in non-Indigenous people in 2009.50 There are no data for urban-dwelling Aboriginal and Torres Strait Islander peoples, but a national multicentre study that included Central Australia, Darwin and the Torres Straits found that among children newly presenting to a respiratory service with chronic cough, Aboriginal and Torres Strait Islander children have a significantly higher incidence of bronchiectasis than non-Indigenous children (29.4% versus 6.7%, respectively; P=0.001).51

In the NT Top End, Aboriginal adults with bronchiectasis have significantly poorer outcomes (poorer lung function, more exacerbations and earlier death) and higher comorbidities than non-Aboriginal patients.52 In contrast, in NT Top End children, there is no difference in severity or outcomes between Aboriginal and non-Aboriginal children,13 which is likely related to close attention to secondary prevention factors, because it is now widely accepted that early diagnosis with optimised treatment prevents disease progression and can even reverse radiological bronchiectasis.1 For the same reason, in Australia, there is no reported mortality in children with bronchiectasis. However, mortality from bronchiectasis is exceptionally high in Aboriginal and Torres Strait Islander adults, with a gap of approximately 20 years earlier than in non-Indigenous Australians with bronchiectasis, a substantial disparity.13 Indeed, a Central Australian study reported that 34% of the cohort died at a median age of 42.5 years,49 almost certainly contributed to by a lack of effective secondary prevention (suboptimal clinical care).53

Diagnosis and related conditions

Bronchiectasis is heterogeneous and has, or is associated with, many aetiologies.1,3,54 Although the most common cause of bronchiectasis in Aboriginal and Torres Strait Islander people is postinfectious,13,47,49,52 everyone diagnosed with bronchiectasis should be thoroughly investigated for underlying aetiology, which potentially impacts on treatment.2,3,33 Investigation to identify the cause of bronchiectasis is considered to be a marker of good-quality clinical care and reflects recommendations as per current clinical practice guidelines. Although human T-cell lymphotropic virus type 1 (HTLV-1) infection has been reported to be the cause of bronchiectasis in NT adults,49 this is not widely accepted as a cause of bronchiectasis and was not found in a study of 288 NT children with bronchiectasis.13

Bronchiectasis can co-exist with other chronic airway diseases (eg asthma and COPD) and/or be misdiagnosed as other conditions.3,55 Bronchiectasis was detected in 40% of a cohort of newly referred adults with ‘difficult asthma’.56 A meta-analysis of 18 studies found that the prevalence of bronchiectasis in COPD was 54% (range 25–69%).57 Another meta-analysis of 14 observational studies described comorbid bronchiectasis in COPD increased the risk of exacerbation (relative risk [RR] 1.97; 95% CI 1.29–3.00), isolation of a potentially pathogenic microorganism (RR 4.11; 95% CI 2.16–7.82), severe airway obstruction (RR 1.31; 95% CI 1.09–1.58) and mortality (RR 1.96; 95% CI 1.04–3.70).58 That meta-analysis also reported a wide range of co-existent bronchiectasis (4–72%).58 One NT study reported that 32% of Aboriginal and Torres Strait Islander people with COPD have bronchiectasis.59

The morbidity and lived experience of people with bronchiectasis includes increased hospitalisation, excess days off work/school, poor quality of life and complications associated with chronic cough.1,3,54 Bronchiectasis-associated complications extend beyond the respiratory system.60 Chronic endobronchial infection, which is present in CSLD and bronchiectasis, is an independent risk factor for atherosclerosis, coronary heart disease and coronary deaths.61–63 Other complications include cardiac, systemic (eg reduced wellbeing), sleep64 and mental health (anxiety and depression) problems.3,65

Primary prevention

Primary prevention of bronchiectasis/CSLD requires prevention and comprehensive treatment of severe and recurrent ARIs in children. Aboriginal and Torres Strait Islander children hospitalised with pneumonia are 15-fold more likely to develop bronchiectasis than non-Indigenous children, and recurrent pneumonia increases the risk.5 One cohort study reported that 25.6% of Aboriginal children hospitalised for lobar pneumonia had a new diagnosis and treatable chronic respiratory illness (18% bronchiectasis) on follow-up.6 In a follow-up study of Aboriginal children hospitalised with bronchiolitis, the presence of cough at three to four weeks after discharge increased the odds of having bronchiectasis diagnosed by 13 months.7 Differentiating between bronchiectasis as a cause or consequence of an earlier admission diagnosed as pneumonia or bronchiolitis can be problematic. Nevertheless, given the likely link between acute lower respiratory infections (ALRIs) and bronchiectasis,5,7 as well as the association between the duration of chronic cough and lung function decline in adults,21 it is good clinical practice for all children and adults with ALRIs to be reviewed in primary care at least three to four weeks after the ARI, especially after hospitalisation. They should be screened for the presence of chronic cough and the persistence of other respiratory symptoms and signs (eg wheeze and crackles on chest auscultation). 

When chronic (more than four weeks) wet cough is present in children, appropriate antibiotics (covering common respiratory pathogens: Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae) are recommended. A systematic review and guidelines support this approach.8,9,18 In a Cochrane review, progression of illness, defined as the requirement for further antibiotics, was significantly lower in children with chronic wet cough (more than four weeks) who received antibiotics than in those who did not receive antibiotics (the control group).10 Data are unclear in adults because protracted bacterial bronchitis is still unrecognised, but there is now emerging evidence that this is also the case in adults.66 

The most common symptom of bronchiectasis is chronic cough.1 Data show that Aboriginal people and Torres Strait Islander children who are newly referred with chronic cough have a significantly higher likelihood of bronchiectasis on further assessment.51 Because chronic cough may be considered ‘normal’, it tends to be underreported by Aboriginal people.41,67 In children, triggers for referral to a specialist include:

  • more than three episodes of chronic (more than four weeks) wet cough per year responding to antibiotics
  • chest X-ray abnormality persisting for more than six weeks following appropriate therapy (Box 2).

Cohort data have shown that approximately 80% of newly diagnosed adults with bronchiectasis were symptomatic since childhood, and that the duration of chronic cough (the most common symptom of bronchiectasis1) is inversely related to lung function at diagnosis.21 This means that the longer the duration of cough, the poorer the lung function at diagnosis based on forced expiratory volume at one second (FEV1).21

Immunisation (pneumococcal, influenza) is effective in preventing severe and recurrent ARIs.68,69 However, despite high immunisation rates, one in five Aboriginal and Torres Strait Islander NT infants are still hospitalised with an ALRI in their first year of life.70 Healthy nutritional status is essential for optimal immune efficiency.25 Although vitamin D deficiency is associated with increased ARI in Aboriginal and Torres Strait Islander children23,26 and poorer clinical outcomes in adults with bronchiectasis,24 the data are currently insufficient to warrant universal screening. In NT children with bronchiectasis, vitamin D deficiency was rarely present.13

Exposure to in utero tobacco smoke is associated with lower birth weights, increased ARI and other respiratory morbidity.28,29 Breastfeeding is protective against the development of bronchiectasis, whereas being born premature or small for gestation age are risk factors.5 Primary prevention strategies to reduce these factors and increase breastfeeding would be beneficial. The association between poor hygiene and the excessive burden of infections (especially respiratory and gastrointestinal) has been well demonstrated.71,72 However, data specific to Aboriginal and Torres Strait Islander peoples are sparse.71 Although hand hygiene is widely recommended, the evidence for effectiveness in reducing respiratory infections is heterogeneous and inconsistent.73

Environmental air pollutants37 exacerbate chronic respiratory disorders and constitute an additional risk factor for those with CSLD or bronchiectasis. Living near a major road has been associated with increased mortality in bronchiectasis (hazard ratio for each 10-fold increase in distance from a major road 0.28; 95% CI 0.10–0.77).37 Young children74 and those aged >65 years may be more susceptible to the adverse effects of air pollution.38 

Secondary prevention

Frequent exacerbations of bronchiectasis, especially when hospitalisation is required, are a risk factor for lung function decline.14,75 Thus, when exacerbations are frequent (three or more per year non-hospitalised episodes, or two per year hospitalised episodes), consider the use of maintenance antibiotics in collaboration with specialists.2 

Worldwide, including in Australia,76 services for bronchiectasis are under-resourced compared with other chronic respiratory diseases, and this is accentuated for Aboriginal and Torres Strait Islander people.18 Effective clinical management reduces both short- and long-term morbidity and premature mortality associated with bronchiectasis.13,77,78 There is increasing evidence that intensive treatment of children who either have bronchiectasis or are at risk of developing severe bronchiectasis prevents poor lung function in adulthood.1,2,65,78 

Optimal overall management and treatment can potentially prevent chronic respiratory disease in a substantial number of people,1,2 including Aboriginal and Torres Strait Islander people.79 Primary care health providers can play a crucial role in the recognition and early detection of disease,79 as well as in long-term management,12,80 because optimal management prevents complications and premature death. This includes monitoring, an essential secondary prevention strategy recommended in guidelines.2,3 In addition, those with airway diseases (eg COPD and asthma) where bronchiectasis overlaps should be assessed for bronchiectasis symptoms and evaluated in accordance with evidence.1 Several prognostic scores (eg FACED score81) for adults with bronchiectasis are now available but have limited value in Aboriginal and Torres Strait Islander people with bronchiectasis.43 Thus, secondary prevention is of utmost importance. Despite all the challenges, Aboriginal and Torres Strait Islander people with bronchiectasis should have access to best-practice care and the same treatment goals1 as non-Indigenous people.

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  7. McCallum GB, Chatfield MD, Morris PS, Chang AB. Risk factors for adverse outcomes of Indigenous infants hospitalized with bronchiolitis. Pediatr Pulmonol 2016;51(6):613–23. doi: 10.1002/ppul.23342.
  8. Chang AB, Oppenheimer JJ, Weinberger MM, et al. Management of children with chronic wet cough and protracted bacterial bronchitis: CHEST guideline and expert panel report. Chest 2017;151(4):884–90. doi: 10.1016/j.chest.2017.01.025.
  9. Chang AB, Oppenheimer JJ, Weinberger M, Rubin BK, Irwin RS. Children with chronic wet or productive cough – treatment and investigations: A systematic review. Chest 2016;149(1):120–42. doi: 10.1378/chest.15-2065.
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  18. Morice AH, Millqvist E, Bieksiene K, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J 2020;55(1):1901136. doi: 10.1183/13993003.01136-2019.
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  24. Chalmers JD, McHugh BJ, Docherty C, Govan JR, Hill AT. Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis. Thorax 2013;68(1):39–47. doi: 10.1136/thoraxjnl-2012-202125.
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