O7. Co-morbidities & drug safety

O7.1 Aspiration

Aspiration of food and liquid is common in COPD and may be the cause of recurrent exacerbations and complications, such as pneumonia and patchy pulmonary fibrosis.

Diagnosis is usually easy with an adequate history from patients and their partners or carers. Dry biscuits and thin fluids cause the most difficulty.  Confirmation rests with assessment by a speech therapist/ pathologist and videofluoroscopy.

Treatment involves retraining in safe swallowing techniques, which may include:

• avoiding talking when eating;

• sitting upright;

• taking small mouthfuls;

• chewing adequately;

• drinking with dry foods;

• using a straw; and

• drinking thickened fluids.

O7.2 Gastro-oesophageal reflux

In patients with COPD, hyperinflation, coughing and the increased negative intrathoracic pressures of inspiration may predispose to reflux, especially during recumbency and sleep. A cross-sectional questionnaire-based study found an increased rate of gastro-oesophageal reflux was associated with increased COPD exacerbations¹¹⁹ but this finding has not been addressed prospectively. Microaspiration of oesophageal secretions (possibly including refluxed gastric content) is a risk, especially with coexistent snoring or OSA. Reflux and microaspiration exacerbate cough, bronchial inflammation and airway narrowing.

Diagnosis may be confirmed by 24-hour monitoring of oesophageal pH, modified barium swallow or gastroscopy. However, a therapeutic trial of therapy with H₂ -receptor antagonists or a proton-pump inhibitor may obviate the need for invasive investigations. Lifestyle changes, including stopping smoking, limiting food intake within 4 hours of bed-time, reduced intake of caffeine and alcohol, weight loss and exercise, will also help. Elevation of the head of the bed is also recommended.

Randomised controlled trials of these interventions are required.

O7.3 Alcohol and sedatives

Patients with COPD have impaired gas exchange and an exaggerated fall in PO₂ with recumbency and sleep onset.^120,121 Excessive use of alcohol and sedatives exacerbates this and predisposes to sleep-disordered breathing. Heavy cigarette smoking is associated with misuse of other substances in many individuals. Nicotine, caffeine and alcohol also predispose to gastro-oesophageal reflux.

O7.4 Sleep related breathing disorders

COPD has adverse effects on sleep quality, resulting in poor sleep efficiency, delayed sleep onset, multiple wakenings with fragmentation of sleep architecture, and a high arousal index. Arousals are caused by hypoxia, hypercapnia, nocturnal cough and the pharmacological effects of methylxanthines and beta-adrenergic agents.¹²² Intranasal oxygen administration has been shown to improve sleep architecture and efficiency, as well as oxygen saturation during sleep.¹²⁰

Indications for full diagnostic polysomnography in patients with COPD include persistent snoring, witnessed apnoeas, choking episodes and excessive daytime sleepiness. In subjects with daytime hypercapnia, monitoring of nocturnal transcutaneous carbon dioxide levels should be considered to assess nocturnal hypoventilation. Patients with COPD with a stable wakeful PaO₂ of more than 55 mmHg (7.3 kPa) who have pulmonary hypertension, right heart failure or polycythaemia should also be studied. Overnight pulse oximetry is also useful in patients with COPD in whom long-term domiciliary oxygen therapy is indicated (stable PaO₂ < 55 mmHg, or 7.3 kPa) to determine an appropriate oxygen flow rate during sleep.

The overlap syndrome: The combination of COPD and obstructive sleep apnoea (OSA) is known as the "overlap syndrome". The prevalence of COPD in unselected patients with OSA is about 10%, while about 20% of patients with COPD also have OSA.¹²¹  Patients with COPD who also have OSA have a higher prevalence of pulmonary hypertension and right ventricular failure than those without OSA.¹²¹ There is frequently a history of excessive alcohol intake. While oxygen administration may diminish the degree of oxygen desaturation, it may increase the frequency and severity of hypoventilation and lead to carbon dioxide retention.

As in other patients with OSA, weight reduction, alcohol avoidance and improvement of nasal patency are useful in those with COPD. Nasal continuous positive airway pressure (CPAP) is the best method for maintaining patency of the upper airway and may obviate the need for nocturnal oxygen. If nasal CPAP is not effective, then nocturnal bilevel positive airway pressure ventilation should be considered, although the benefits of this in chronic stable COPD remain to be established. The role of other OSA treatments, such as mandibular advancement splinting, remains to be evaluated in the overlap syndrome.

O7.5 Osteoporosis

Patients with COPD are at increased risk for fracture due to the disease itself, the use of high dose glucocorticoids and coexisting risk factors such as hypogonadism (induced by glucocorticoid therapy itself in high doses in men and women), immobilization reduced muscle mass and other factors. These patients may have reduced bone mineral density (BMD) due to a reduction in bone formation and perhaps increased bone resorption, the latter being primarily due to the underlying disease itself.

There is little evidence of a deleterious effect of inhaled glucocorticoid at conventional doses (<2, 200 mcg/day) on fracture risk. However, triamcinolone was associated with reduced BMD in the Lung Health Study¹²³ [evidence level II]. Australian Guidelines on the prevention and treatment of osteoporosis, including glucocorticoid-induced osteoporosis have been published.¹²⁴ Information on the current subsidies relevant to these drugs can be found on the website of the Pharmaeceutical Benefits Scheme (www.pbs.gov.au/html/healthpro/search/results?atc-code=M05B&publication=GE) Higher doses of inhaled glucocorticoids are associated with suppressed biochemical markers of remodelling but data on BMD and fractures at these doses are not available¹²⁵ [evidence level I].

Despite the lack of evidence, management strategies in individuals taking long term glucocorticoid therapy should include investigation of fracture risk including bone densitometry, assessment of vitamin D status, and other risk factors such as coexisting illnesses that may influence the skeleton (e.g. primary hyperparathyroidism). In individuals with low BMD at onset and in those taking more than 10-15mg of prednisolone per day or who have several risk factors for osteoporosis and whose BMD is <1.5 standard deviations below the young adult mean, treatment should be considered.

Evidence for fracture risk reduction is available for alendronate, risedronate, etidronate and parathyroid hormone. There is no evidence that calcitriol reduces fracture risk and some evidence to the contrary, so that the use of this drug is not recommended.¹²⁶ However, most patients in these studies did not have respiratory disease. Although calcium supplementation has not been demonstrated to reduce the risk of fracture in osteoporosis, a reduction in remodelling rate with some possible benefit in slowing bone loss is possible so calcium supplements are appropriate. Any deficiency of vitamin D should be corrected with supplements.