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COPD and bronchiectasis — the hidden danger

Case report 1

A 65-year-old female patient with stable COPD presents to the GP practice looking for a renewed script. She mentions excessive half-cupful of purulent sputum production and stable dyspnoea on inclines (mMRC 1).

Background history has COPD GOLD Grade C diagnosed in 2007, and four presentations requiring aminopenicillins and steroids in the past year for an acute exacerbation of COPD (AECOPD), including one hospitalisation. She has a previous 20 pack-smoking exposure. Pulmonary auscultation reveals bilateral basal crackles. How would you manage this patient?

Management

Despite the long-standing diagnosis of COPD, it is important to screen the patient for features of bronchiectasis in light of the excessive sputum production and crackles on auscultation. Recognition of bronchiectasis is important, as it has distinct therapeutic strategies, which add to regular COPD management. Excessive sputum production is a feature of COPD, as well as bronchiectasis. It is recommended that the clinical history quantifies patients’ sputum volume (eg, one tablespoon ≈ 15mls) and record sputum character. COPD patients usually have a chronic cough, with small amounts of mucoid sputum (less than 50mls/day). Crackles on auscultation are not a feature of COPD.

Bronchiectasis and COPD are both inflammatory airway diseases. Despite numerous trials demonstrating a very high prevalence of bronchiectasis in COPD, a causal relationship between COPD and bronchiectasis has not been demonstrated in prospective fashion. It is hypothesised that chronic airway colonisation with pathogenic microbes leads to chronic bronchial infection, which drives formation of bronchiectatic airways.

Similar radiological features of early bronchiectasis with bronchial wall-thickening have been noted in chronic bronchitis as part of COPD evolution. At a cellular level, airway biopsies in both diseases share similar inflammatory chemokines, like IL-8 and pro-inflammatory cytokines like TNF-α. In earlier studies of lung flora in COPD patients, the commonest pathogenic micro-organisms isolated were Haemophilus influenzaeStreptococcus pneumoniae and Moraxella catarrhalis.

Pseudomonas aeruginosa is a pathogenic micro-organism more commonly associated with bronchiectasis. Pseudomonas aeruginosa is also frequently isolated in patients with more severe COPD, predictably in poorer lung function subgroups and frequent exacerbators. There is evidence that chronic Pseudomonas aeruginosa colonisation has been linked with accelerated decline in lung function, increased hospital admissions and poorer health-related quality of life.

Despite the increasing awareness of COPD-bronchiectasis overlap, both diseases have separate diagnostic criteria. COPD is a partly a physiological diagnosis confirmed by demonstration of expiratory airflow obstruction on spirometry. Bronchiectasis demonstrates typical radiological changes on CXR or high-res CT thorax.

Case report 2

An 85-year-old man with Grade B COPD is in a general outpatients clinic. He has dyspnoea on exertion, mMRC 2. Background history includes osteoarthritis and glaucoma. He is currently on 50mcgs salmeterol and 1,000mcgs fluticasone, using a pressurised metered-dose inhaler (pMDI) and 18mcgs tiotropium using a dry powder inhaler (DPI). The patient’s daughter is with him, as he is sometimes forgetful and she helps him with his medications. He has early-morning stiffness in his hands. How would you consider device selection for inhaled pharmacotherapy in this patient?

Management

With the growing armamentarium of inhaled pharmacotherapy, it is imperative that the inhaler device choice is individualised to the patient. Inhaled pharmacotherapy is currently delivered in pMDIs, DPIs, breath-actuated pressurised MDIs (baMDI), nebulisers, and soft mist inhalers (SMI).

After deciding on COPD severity and suitable pharmacotherapy, consider the patient’s device preference, cognitive abilities, hand function, ability to co-ordinate inspiration and hand actuation before selecting a device (see Table 1). Including a patient’s device preference in your consideration leads to shared decision-making and increased adherence. For example, a patient might prefer using a similar device (eg, DPI) for all their inhaled medications. With the increasing choice of inhaled medications in the Irish market (see Table 2), it is important to have a basic understanding of the various inhaler costs and reimbursements on the Drug Payment Scheme to avoid non-adherence due to financial reasons (Table 1 and Table 2).

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Table 1: Suggested standard procedure in choosing inhaler device

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Table 2: Inhaler devices currently available in Ireland

Discussion

The most recent edition of the European Lung White Book highlighted that Ireland has a mortality rate from acute exacerbations of COPD (AECOPD) of 27.8 per 100,000 population, in contrast to the overall EU rate of 18 per 100,000 population. The Book also warned that COPD mortality would increase in the next two decades, while mortality from other respiratory diseases will decline. More than half of recently-discharged COPD patients with AECOPD were shown to need readmission within one year.

Strategic management during stable COPD is crucial to improving symptoms, lung function and, in particular, reducing exacerbations. In this regard, there has been a surge in improved therapies targeting the airflow obstruction in COPD, mediated by the parasympathetic muscarinic receptor (anti-muscarinic/cholinergic agents) and in improving bronchodilation via the β2 adrenergic-receptors (β2 agonists).

The importance of device selection in delivering these inhaled medications is paramount to treatment success. Good compliance is negated by unintentional non-adherence due to ineffective inhaler technique.

COPD is associated with significant comorbid diseases that predict increased hospitalisations and mortality and indicate benefit from disease-specific therapies. It is important to recognise the impact of often-undiagnosed pulmonary comorbid diseases with COPD, as failure to diagnose same can significantly alter the choice of therapy.

Bronchiectasis is one of these conditions that often goes unrecognised. A recent meta-analysis showed that in 881 patients with COPD, there was a mean prevalence of bronchiectasis of 54.3 per cent (range 25.6 to 69 per cent). Patients with COPD-bronchiectasis had more frequent exacerbations, poorer lung function and chronic colonisation, with higher rates of Pseudomonas aeruginosa and other more virulent G-ve bacilli. Bronchiectasis is a risk factor for all-cause mortality in COPD. Case report 1 on this page addresses the concomitant diagnosis of bronchiectasis in COPD . 

Management of COPD-bronchiectasis in a stable state

Good bronchopulmonary hygiene with regular airway clearance should be emphasised. We recommend hand-held devices that generate positive expiratory pressure devices, like the Flutter valve and Acapella device, to facilitate mobilisation of tenacious mucus. Between 6-to-7 per cent hypertonic saline is beneficial when nebulised before performing airway clearance.

There should be a low threshold for referral to a respiratory specialist to screen for secondary causes of bronchiectasis, eg, hypogammaglobulinaemia, alpha1-antitrypsin testing and cystic fibrosis variants, which may have their own specific interventions.

Role of prophylactic antibiotics in bronchiectasis in a COPD patient

Prophylactic macrolides have immunomodulatory and inhibitory effects on biofilm formation in both COPD and bronchiectasis.

A biofilm is a structured community of bacterial cells enclosed in a self-produced protective matrix, which adheres to human cells. The inhibitory effect on biofilms is beyond antimicrobial effects as, despite macrolides theoretically having no efficacy in Pseudomonas infections, it has demonstrated equal efficacy in reducing exacerbations in the Pseudomonas subgroup. Initially studied in CF-related bronchiectasis and then in non-CF-related bronchiectasis, a Cochrane systematic review has shown efficacy of continuous azithromycin at 250mcg daily in COPD patients in reducing the rate of AECOPD.

Patients should be screened for hearing loss before and during long-term macrolide therapy. Regular audiometry or ENT review can be considered, depending on reported symptoms.

Prospective data showing increased macrolide resistance suggests that prophylaxis only be reserved for recurrent, severe exacerbators, particularly patients requiring repeated hospitalisations.

Other options in patients with chronic Pseudomonas aeruginosa colonisation include regular inhaled colomycin, gentamicin, tobramycin and ciprofloxacin, all of which have shown varying benefits in reducing bacterial load and overall systemic inflammation (see Figure 1).

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Figure 1: Bacterial biofilm formation during an infection

Antimicrobial managements of infective exacerbations in a COPD patient with bronchiectasis

To prevent antimicrobial failure, patients with COPD-bronchiectasis overlap should have longer courses of antibiotics, including longer courses of intravenous antibiotics, if hospitalised. British Thoracic Society guidelines suggest 14 days of antibiotics for treating bronchiectasis exacerbations, in contrast to COPD regimens, which are usually five-to-seven days.

Shorter courses in COPD-bronchiectasis may be ineffective. Sputum purulence can guide treatment length.

What considerations should you make in selecting an inhaler device for the patient in case report 2?

Case report 2 above explores some issues around inhaler devices for inhaled pharmacotherapy in stable COPD patients.

A patient with significant osteoarthritis in their hands is likely to have reduced manual dexterity. Be mindful of a patient’s ability to handle a specific inhaler, including grip strength. The patient in this case might be unable to effectively actuate an inhaler device to use it appropriately. This manual dexterity is particularly important in pressurised MDIs, which require the patient to synchronise their inspiratory breath with actuating the device.

Executive dysfunction is another criteria that leads to inappropriate inhaler technique. Executive function is the complex cognitive processing to co-ordinate several actions to reach a particular goal. It is associated particularly with reduced ability to co-ordinate one’s inspiratory breath to the necessary hand manoeuvre to actuate the inhaler device. Furthermore, patients with executive dysfunction are unlikely to master the multi-step commands in a pressured MDI, like co-ordinating breath-hand manoeuvres, slow and gradual inspiration and then the breath-hold. Screen for executive dysfunction by looking for reduced cognitive ability, eg, MMSE <23, an ability to manage one’s own medications, or a history of requiring help with activities of daily living.

What about inspiratory flow rate?

Unlike tablets, the respiratory patient is required to have an adequate inspiratory flow rate to successfully inhale medication. This is most important with dry powder inhalers (DPIs) that are not pressurised, and hence rely on the patient’s effort. In severe COPD, patients have hyperinflated lungs, leading to reduced inspiratory capacity. Ideally, every clinic should have adequate supply of device placebos to facilitate rational prescribing by specifically checking for an adequate inspiratory flow rate. In non-responders to inhaled therapy, it is possible to objectively measure the inspiratory flow rate quickly using hand-held inspiratory flow meters like the In-Check Dial device.

A common complaint is mouth dryness when either poor technique or reduced inspiratory flow rates lead to increased oropharyngeal deposition. Breath-actuated pMDIs help overcome reduced co-ordination to manage pMDIs when a patient has sufficient inspiratory flow rate. Newer soft-mist inhalers need little co-ordination and some grip strength but achieve high lung deposition due to a longer medication release phase.

Conclusion

Increasing awareness of COPD-bronchiectasis can highlight potential add-on therapeutic strategies to benefit overall COPD outcome. Deciding on pharmacotherapy in COPD is relatively straightforward but inhaler device consideration will maximise the pharmacologic benefit of our prescribed pharmacotherapy.

References available on request

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