Respiratory conditions - quality prescribing strategy: improvement guide 2024 to 2027

7. Bronchiectasis, Persistent Bacterial Bronchitis and Chronic Bronchial Sepsis

Bronchiectasis

Repeated lower respiratory tract infections can be caused by a range of clinical conditions. Bronchiectasis is characterised by the radiological finding of dilated, non-tapering bronchi with thickened walls on a high-resolution Computerised Tomography (CT) scan of the thorax. The associated clinical syndrome is characterised by frequent, usually daily, sputum production and repeated lower respiratory tract infections. It has become evident, however, that the clinical syndrome can be present in the absence of the characteristic CT findings – this clinical syndrome has become known, variably, as Persistent Bacterial Bronchitis, Chronic Bronchial Sepsis, and Bronchiectasis with a normal CT scan.

Severity of radiological bronchiectasis does not correlate well with the severity of symptoms, and a holistic approach should be taken with assessment of bronchiectasis severity, with a number of validated scoring systems available e.g. The Bronchiectasis Severity Score.^[61] Guidance for referral to secondary care can be found in the BTS Guideline for Bronchiectasis in Adults. ^[62]

Summary of recommendations in bronchiectasis

• antibiotic choice should be directed by previous positive cultures - in the absence of previous positive sputum cultures, oral antibiotics to cover common respiratory pathogens are recommended, using local formulary guidance where available
• azithromycin 250mg three times a week is recommended for patients with four or more exacerbations in any 12-month period, usually started after advice from secondary care
• recommend six-month review of effectiveness of mucolytics

Principles of prescribing for Bronchiectasis

There are no licenced treatments for bronchiectasis, other than antibiotics for acute bacterial exacerbations.

There is a growing body of high-quality research for long term treatments for bronchiectasis; recent guidelines from national and international respiratory societies offer evidence-based recommendations for clinicians.^[62],[63]

Airway clearance techniques and adjuncts should be considered, with appropriate instruction from a suitably trained physiotherapist.

Prescribing issues to address

Acute exacerbations

Oral antibiotic therapy should be guided by sputum cultures. Antibiotic choice should not be delayed while culture results are awaited – the choice should be directed by previous positive cultures. In the absence of previous positive sputum cultures, oral antibiotics to cover common respiratory pathogens are recommended, using local formulary guidance where available. The recommended duration is 14 days. Shorter courses may suffice in those with mild bronchiectasis.^[62]

• 1st line - amoxicillin 500mg to 1g three times a day^[62]
• 2^nd line - doxycycline 100mg twice a day

A first positive culture for Pseudomonas aeruginosa in sputum should trigger a discussion with local bronchiectasis specialists to consider eradication therapy.

Long term antibiotics

Azithromycin 250mg three times a week is recommended for patients with four or more exacerbations in any 12-month period, after advice from secondary care. It has the most evidence base. Patients should be made aware of the potential adverse effects:

• tinnitus and hearing loss (which can be reversed if treatment is stopped early)
• prolongation of QTc interval and consequent increased risk of ventricular tachycardia
• anti-microbial resistance

Prior to commencing azithromycin, a mycobacterial culture of at least six weeks should be negative. An ECG should be performed to ensure a normal QTc and a medication check should be carried out to consider interactions, particularly with other medications that may prolong the QTc interval. Liver function tests with six monthly monitoring is recommended.

Azithromycin should be continued during exacerbations requiring antibiotics, except when receiving quinolone antibiotics (ciprofloxacin, levofloxacin, moxifloxacin) in which case the azithromycin should be stopped due to risk of QTc prolongation. Azithromycin is less beneficial in active smokers.^[47]

Clarithromycin 250mg daily can be used as an alternative macrolide for long term prophylaxis of exacerbations.

Doxycycline 100mg daily can be used as an alternative in patients who cannot tolerate, or are not suitable for, long term macrolide therapy.

Check local formulary guidance for area specific recommendations.

Bronchodilator Therapy

Breathlessness is multifactorial in bronchiectasis. A trial of combination bronchodilator containing a long-acting beta₂agonist (LABA) and long-acting muscarinic antagonist (LAMA) can be considered, particularly if the patient has co-existent COPD. The choice of LABA/LAMA should be based on the inhaler technique of the patient, local and national prescribing guidance.

Inhaled and Oral Corticosteroids

Oral steroids should be avoided in patients with bronchiectasis, unless there is a clear indication for an alternative comorbidity, such as asthma.

Although there is evidence for benefit of inhaled corticosteroids (ICS) for patients with COPD and elevated eosinophil counts, studies in bronchiectasis with eosinophilia are yet to report. Patients with concomitant COPD and bronchiectasis should receive ICS in line with current COPD guidance. Patients with isolated bronchiectasis and an eosinophilia may benefit from a trial of ICS. Advice from a bronchiectasis expert is strongly recommended.

Nebulised Saline

Nebulised saline can be considered for sputum clearance in bronchiectasis if airways clearance techniques are not effective. Available concentrations are 0.9% (“Normal” saline), and 3%, 6%, 7% (hypertonic saline). Perform an airway reactivity challenge test when inhaled mucoactive treatment is first administered.^[62]

There is currently no evidence to recommend any concentration of saline over any other, though side effects may limit the higher concentrations in use. The dosing schedule is four ml of saline nebulised two to four times per day.

Oral Mucolytics

There is currently no high-quality evidence base for oral mucolytic therapy in people with bronchiectasis, however carbocisteine and acetylcysteine are widely used in Scotland to improve sputum clearance. Their use should be accompanied by support for airway clearance techniques. Acetylcysteine has once daily dosing which may assist with adherence to therapy. At least annual review of effectiveness of oral mucolytics is strongly recommended if either agents are trialled in any individual. If a mucolytic is started in secondary care it can be reviewed in either primary or secondary care for effectiveness. See Chart 8 for prescribing of mucolytics in Health Boards.

Acetylcysteine should not be given at the same time of day as antibiotic therapy as it potentially reduces antibiotic absorption.

Fungal infection

Fungal infection can occur in advanced bronchiectasis. Cultures for fungal infection, and serology for aspergillus, should be sought in cases of severe bronchiectasis refractory to other treatment. Results suggestive of the presence of fungal infection warrant immediate discussion with a bronchiectasis and/or fungal infection specialist. Antifungal treatment for aspergillus disease should be co-ordinated through a dedicated multidisciplinary team.

To prescribe most effectively for individuals with bronchiectasis the ‘what matters to you?’ principles and the Polypharmacy 7-Steps approach are recommended. Table 4 outlines the main principle for treating patients with bronchiectasis.

Table 4: Principles of treating patients with bronchiectasis

Polypharmacy review 7-Steps / Bronchiectasis

1 What matters to the patient?

• Ask the patient what matters to them?
  • chronic sputum production
  • frequency of exacerbations
  • breathlessness
  • cough
• Ask patient to complete PROMs (questions to prepare for my review) before their review
• How does the condition affect patient’s day to day life / activities
• Side effects of medicines versus benefit
• Patient’s awareness of the reason for taking medications
  • antibiotics for exacerbations
  • preventative treatments
  • inhaled therapies
  • mucolytics
• A holistic Polypharmacy 7-Steps approach is recommended to ensure treatment is optimised giving consideration to comorbidity

2 Identify essential drug therapy

• Confirm ongoing need for and effectiveness of medication and screen for side effects
  • all patients on long term macrolide should have assessment of hearing/tinnitus

3 Does the patient take unnecessary drug therapy?

• Assess adherence and ensure patient understands treatment regime
• Is there evidence of benefit from taking the treatment, e.g. reassuring physiology, maintaining exercise tolerance
• Assess the benefit of mucolytic therapy – is it warranted?

4 Are therapeutic objectives being achieved?

• Frequency of infective exacerbations
  • is there a role for long term antibiotic therapy?
• Ensure regular monitoring of physiology
• Ensure sputum cultures are up to date. Discuss sputum cultures, including annual nontuberculous mycobacterial (NTM) cultures
• Check antibiotic course duration is appropriate
• Vaccinations should be offered if not up to date (influenza, pneumococcal, DTaP (if not vaccinated in adolescence) and Covid-19)
• Patients should be encouraged to engage in appropriate physical activity. Social prescribing such as exercise dependant on ability, singing classes
• Discuss Pulmonary Rehabilitation (PR)
• Smoking cessation should be advised and the adverse effects of smoking on children highlighted. Offer appropriate support. Signpost patients to the NHS inform Quit Your Way Scotland website (which includes community pharmacy services)
• Weight reduction is recommended in obese patients (BMI >30)
• Nutritional advice and support will be necessary in those with a BMI less than 20

5 Does the patient have ADR/ side effect or is at risk of side effects?

• Ensure regular drug monitoring as per local protocol
• Review potential drug interactions which can potentiate side effects
• Discuss side effect profile with perceived benefit of treatment
• Confirm antibiotic allergy/side effect profile
  • Consider referral for penicillin allergy de-labelling52 if available locally
• Yellow card reporting of ADRs

6 Sustainability

• Ensure drugs are either within current guidelines or have been discussed at a specialist multidisciplinary team meeting
• Course length of antibiotics?

7 Is the patient willing and able to take drug therapy as intended?

• Are at-home antibiotics appropriate for the patient to enable self-management?
• Make patient aware of support information
• Non-attenders should be followed up – alternative strategies to encourage engagement may be required, (e.g. through community pharmacy / Near Me / telehealth acknowledging limitations
• Agree with the patient arrangements for repeat prescribing. Signpost to Medicines Care and Review (MCR) service in community pharmacy
• Ask patient to complete the post-review PROMs questions after their review

Bronchiectasis Case Study

Background Details - (Age, Sex, Occupation, baseline function)

• 58-year-old female
• Works as a secondary school teacher
• Still working full time

History of presentation/ reason for review

• Referred by primary care healthcare professional due to productive cough, asking if she has COPD.
• On presentation at clinic, has had two episodes of chest infection requiring antibiotics in last six months. On both occasions, sputum grew Haemophilus influenzae
• Daily production of yellow sputum
• Minimal breathlessness
• No chest pains

Current Medical History and Relevant Comorbidities

• Severe chest infection at eight years (spent three months in hospital)
• Was ‘chesty’ through adulthood

Current Medication and drug allergies (include OTC preparation and Herbal remedies)

• No current medication
• Had been given SABA inhaler with no benefit
• No drug allergies

Lifestyle and Current Function (inc. Frailty score for >65yrs) alcohol/ smoking/ diet/ exercise

• Never smoked
• Drinks alcohol on special occasions
• Enjoys walking holidays

Results e.g., biochemistry, other relevant investigations or monitoring

• Localised bronchiectasis (right lower lobe), otherwise normal
• No radiological evidence of NTM pulmonary disease
• Spirometry is normal
• Mycobacterial cultures were negative for NTM

Most recent consultations

First consultation:

• Given the diagnosis of localized bronchiectasis, likely due to childhood pneumonia. No diagnosis of COPD.
• Given instruction in airway clearance techniques by specialist respiratory physiotherapist.
• Commenced on a mucolytic to assist sputum expectoration
• Pulmonary Function Test (PFTs) showed no diagnosis

Follow up 3 months:

• Significant improvement in her ability to clear sputum
• Improvement of day-to-day symptoms reported
• However further chest infections requiring antibiotics
• Discussion regarding long term azithromycin treatment
  • consented to risks of reversible tinnitus / hearing loss associated with long term macrolide use
  • ECG carried out, showing normal QTc of 405
  • advised to continue azithromycin when on other antibiotics except quinolones
• Azithromycin 250mg Monday / Wednesday / Friday commenced

Follow up 6-month review:

• Patient reported no further chest infection since commencing azithromycin
• Routine sputum samples continued to be negative
• Repeat mycobacterial culture was negative
• After discussion azithromycin has been continued long term with good effect

Key concepts in this case

• Confirm diagnosis of bronchiectasis to allow appropriate management
• Sputum management with mucolytics and sputum clearance techniques
• Use of long-term azithromycin for regular exacerbations and discussion of side effects