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Introduction
Age-related changes in the respiratory system
Treatment options in the elderly: managing airways in chronic disease
Managing acute exacerbations: is NIV an option?
Conclusion
References
Introduction
Chronic obstructive pulmonary disease (COPD) is thought to affect more than 200 million people worldwide, and is expected to become the third leading cause of death by 2020.1,2,3 As the prevalence of COPD rises significantly in the 6th decade and beyond, it is increasingly recognised as a disease of the elderly as the population ages.4
In the older patient respiratory function is affected by both anatomical and physiological modifications caused by ageing. There is an increasing body of evidence that describes COPD as the manifestation of accelerated lung ageing and there is growing support of the close relationship between ageing and chronic inflammatory diseases.1,2 This paper reviews changes associated with normal physiological ageing and COPD, and highlights the care needed in diagnosis and selection of treatment options in an elderly population.
Despite this general increase prevalence, estimates show considerable variability across populations. It is suggested that this may result from the differential effects of risk factors rather than physiological differences within different ethnic groups or genetic factors.5
There is undoubtedly a rise in the prevalence of COPD in the older population in the UK, >10% in those aged over 40 years.2 According to NICE, approximately 2 million people remain undiagnosed and most patients are not diagnosed until they are at least in their fifties.6
The mainstay of treatment for COPD remains inhaled drugs, which are usually administered via meter dosed inhalers. The physical and cognitive changes that are common in the elderly, particularly those aged ≥75 years, can interfere with the proper administration of inhaled therapies. This can result in insufficient dosing and inadequate treatment. In the long term this jeopardises health outcomes, reduces quality of life and adds to the economic burden of COPD.7
The impact of using long-term inhaled steroids also needs to be considered in a frailer population and bone density, diabetes management and excess bruising need to be monitored and managed appropriately. A holistic approach needs to be taken within this population to ensure efficacy of treatment and avoid complications.
Age-related changes in the respiratory system
The changes that occur with ageing are complex, but characterised by a decline in FEV1, a reduction in muscular strength and an increase in inflammatory cells in bronchial tissue. These mechanical and cellular changes mimic COPD and can cloud the ability to diagnose obstructive disease in addition to exacerbating any pre-existing disease.
The change in FEV1 is significant and mirrors the increase in obstruction seen in COPD leading to a hypothesis that COPD represents an acceleration of the ageing process. Hankinson et al8 studied the spirometry results of 4,634 lifetime non-smoking US adults without a diagnosis or symptoms of chronic pulmonary disease and found that both men and women demonstrated a reduction of forced expiratory volume in one second (FEV1) of about 200-300 mL every decade between the ages of 20 and 70 years. A salient finding was that at age 70 years, the expected FEV1/FVC ratio would be approximately 74%. This is a value approaching the 70% criterion used for diagnosing significant obstruction.
Fletcher and Peto described loss of 50-100mls in FEV1/year in those with COPD (compared to 20mls/ year in ageing).2 This should be kept in mind when interpreting spirometry reports, although prediction equations are now available for an age range of up to 95 years that include appropriate age-dependent lower limits of normal.9
The main difference at a cellular level between ‘senile emphysema’, which describes loss of elasticity with age, and COPD, is that there is destruction of alveolar walls and fibrosis of the small airways in the latter.4,10 This reduces the ability of the airways to remain open in expiration limiting airflow, which is measured using spirometry (Box 1.)
| BOX 1: DIAGNOSIS OF COPD |
|---|
| Spirometric classification of COPD severity based on post ronchodilator FEV1 |
| Stage I: Mild FEV1/FVC FEV1> 80% expected |
| Stage II: Moderate FEV1/FVC >50% |
| Stage III: Severe FEV1/FVC >30% |
| Stage IV: Very FEV1/FVC Severe FEV1 |
Respiratory muscle mass decline can lead to an inability to ventilate in the face of increasing demands, such as that seen in respiratory disease. The knock on effect of this is a decreased ability to clear mucus from the lungs. Any decrease in the strength of the respiratory muscles will greatly impact an individual’s ability to generate the force required for an effective cough. This was quanitified by Polkey et al11 who showed a 13% decrease in transdiaphragmatic pressure gradients, a surrogate for diaphragm strength, in older subjects (ages 67-81) as compared to younger subjects (ages 21-40).
In older patients with COPD the lung function versus age curve is shifted to the left. As described, overall lung function decreases with age: FVC declines later than FEV1 resulting in a fall in the FEV1/FVC. This should be kept in mind when diagnosing COPD to avoid over diagnosis—the FEV1 must be less than 80% to confirm it (Box 1.).20
All these changes result in predictable functional changes in the ageing lung, and are summarised in Box 2.
Treatment options in the elderly: managing airways in chronic disease
As with younger patients the only therapies with proven impact on mortality are smoking cessation and oxygen therapy. The modified Fletcher-Peto diagram of FEV1 in susceptible smokers highlights that a patient of any age with COPD benefits significantly from smoking cessation as this slows degeneration and decline in the FEV1.21,22 Achieving complete cessation is notoriously difficult with patients and the comparison of the ‘ageing lung’ with the smoke damaged lung has been shown to be a useful and effective psychological tool in the bid to achieve this.23
Studies have shown that continuous oxygen therapy in hypoxaemic patients with COPD improves survival, and survival is directly linked to the number of hours of oxygen used a day. In addition to this, oxygen has also been shown to improve quality of life and exercise tolerance.4 The usual care must be taken that patients are not at risk of developing hypercapnic respiratory failure on commencing oxygen by performing arterial blood gases and monitoring for symptoms of hypercarbia. This sub-set of COPD patients and those that have required either invasive or non-invasive ventilation during an exacerbation, should be considered for domiciliary NIV.24,25 Evidence suggests there the elderly population is just as likely to benefit from this intervention as any other age group.26
Inhaled therapies are the first-line therapeutic intervention and can produce bronchodilation and provide symptomatic relief, but these do not impact significantly upon mortality. Some, such as long-acting anti-muscarinics, can reduce exacerbation frequency with a theoretical effect on reduction in hospital admission and steroid use. Methylxanthines, such as theophylline, should be used with caution in the elderly, due to their narrow therapeutic window and multiple drug interactions.6
It is estimated that 10–25% of patients with COPD respond to corticosteroids, but several reports show a decline in glucorticoid receptor expression with age.2,4 If long-term oral steroid treatment is necessary clinicians should bear in mind that NICE guidelines recommend that those over 65 years of age should be prescribed prophylactic osteoporosis management without monitoring.
In addition to increasing osteoporotic risk and diabetes, the risk of pneumonia also increases with inhaled and oral corticosteroids. A meta-analysis of 24 randomised controlled trials found that the increased risk of pneumonia secondary to inhaled corticosteroids, was not however accompanied by an increase in mortality. It concluded that the elderly and those with more severe disease were at the highest risk of pneumonia.27,28 Chronic low grade ‘Inflamm-ageing’ is thought to lead to development and progression of pulmonary disease in older individuals.26 This and immunosenescence is thought to predispose elderly population to pulmonary infections.28
More research is needed into understanding the molecular mechanisms of COPD in order to develop new therapies.29 On the horizon, but not yet readily available newer anti-ageing molecules, such as Resveratrol, Sirtuin activator, may provide a new therapeutic approach to COPD. These replace endogenous histone deacetylases and sirtuins, which are depleted in smokers and accelerate ageing.2 Until then it remains a clinical decision, on an individual patient basis, to establish the level of treatment that can sufficiently control symptoms without substantially increasing the risk of pneumonia in a group already to susceptible to such infections. Pulmonary rehabilitation has also been shown to improve exercise tolerance and dyspnoea and therefore quality of life.4 This is MDT led and prior to commencing patients should be optimised with regards to comorbidities, for example pain management and effective treatment of angina.
| BOX 2. SUMMARY OF PATHOPHYSIOLOGICAL AND FUNCTIONAL CHANGES IN AGEING LUNG2,4,11 | ||
|---|---|---|
| Pathological changes | Physiological changes | Functional changes |
| Senescent cells enter irreversible growth arrest, with flattened and enlarged morphology with altered gene expression.12 Inflammaging occurs: proinflammatory tissue accumulates which in combination with an increasingly dysregulated immune system causes damage at the cellular level.13 There is a significant decrease in bronchiolar diameter over the age of 40yrs. | There is increasing airways resistance. | Progressive decline in FEV1 over decades. The work of breathing is increased and the metabolic cost is increased |
| Loss of supporting tissue for peripheral airways ‘Senile emphysema’2 Inflammaging: increased numbers of neutrophils secreting neutrophil elastase are found in lower respiratory tracts of healthy elderly individuals.2 |
Decreased elastic recoil and loss of elastin fibres.2 Decreased chest wall compliance (Kyphoscoliosis, arthritis etc.) A reduction in muscle strength and development of kyphosis/ lordosis of the spine result in reduced thoracic expansion.14 |
Increased Residual Volume (RV) and increase in dead space.15 Increased Functional Residual Capacity (FRC) and decreased Expiratory Reserve Volume (ERV). Hyperkyphosis reduces thoracic expansion and increases the work of breathing.16 |
| Overall muscle function in the body decreases by 2% annually as we age.17,18 The changes which cause this to happen at both a cellular and muscular level, result in a gradual shift in the efficacy of muscle function.19 | Diaphragm strength reduced by 25% in healthy elderly individuals compared with young adults. | Decreased respiratory muscle strength, maximum inspiratory and expiratory pressure both decrease with age.
Decreased Vital Capacity (VC), although Total Lung Capacity (TLC) remains quite constant.2 |
| Increase in type III collagen deposition. The site at which small airways close during expiration, shifts more distally with age. | Decrease in oxygen diffusion capacity with age. (small airways closure results in air trapping.) | V/Q mismatch and increased A-A O2 gradient resulting in decline in DLCO (Diffusion capacity of Lung to Carbon Monoxide) 2.03ml/min/mmHg/decade in healthy non-smoking men, and 1.47ml/min/mmHg/decade in healthy non-smoking women.4 |
| Animal models suggest chemo-receptor sensitivity decreases with ageing.11 | Most elderly individuals have reduced ventilator response to hypoxic and hypercapnic challenges.11 | Older individuals generally require greater minute ventilation when performing the same absolute work.11 |
Managing acute exacerbations: is NIV an option?
The answer to this seems to be ‘yes’ although it might at first seem counter intuitive that they would be able to manage a mask as well as younger patients. Rozzinin et al looked at group of patients requiring NIV in a high dependency unit for the elderly— only 12/127 (9.4%) were unable to be tolerate the mask.30,31 A gratifying 78.3% of their patients responding well and showed clinical improvement. Some 25 patients died in hospital and, predictably, the highest mortality was seen in the groups of patients who were disabled and/or demented. Nava et al confirmed this in a group of 82 patients aged over 75—NIV decreased the rate of requiring intubation and mortality.25 An additional measure of effect is the reduced length of hospital stay in those treated with NIV, which is seen across all age groups. There is a low risk of failure in this patient group (10–20%) and proven efficacy—lower mortality and rates of ventilation.23,32
A national audit of the secondary care of patients admitted to hospital with an exacerbation of COPD was conducted in 2003, 2008 and 2014. The 2003 national audit established several predictors of mortality of which; age; pH and performance status (PS) were all of prognostic significance.33 The 2008 audit highlighted that older more hypoxic patients, with a poorer performance status, were receiving NIV, although there was no observed effect on overall mortality.34 Although this data may reflect use of NIV outside of recommended guidelines, to date the use of NIV in this more frail patient group has not demonstrated an adverse effect on mortality, or indeed length of hospital stay.34
The main problem for the patient is one of discomfort caused by the mask. It has the advantage over intubation in that the patient can remove the mask to eat and drink and can still communicate whilst wearing it. It is, however, claustrophobic and can be hard to tolerate for long periods of time. It is also tightly fitting and a balance must be found between a tight fit, which can cause facial necrosis, and allowing for there to be leaks, which compromises the efficacy of treatment. Tolerating the mask is a considerable challenge particularly in those with cognitive impairment or delirium secondary to sepsis. Sedating the patient is not to be encouraged as this can increase the risk of aspiration and also reduces the patient’s ability to co-ordinate their breathing with the pressure changes within the mask.
Farrero et al found most frequent adverse effects of domiciliary NIV mask were minor and similar to previous studies.35 No significant side effects were reported in the elderly and the incidence was similar to that observed in the general population, which is approximately 10%. Although some are as high as 35%, this occurred when NIV was used as treatment for COPD regardless of type 2 respiratory failure.35
Patient selection should be considered carefully: in those who are likely to fail treatment. NIV can be dangerous as it delays time to intubation. Factors that predict NIV failure are a high APACHE II score and acidosis persisting more than one hour after treatment.36 The baseline severity of acidosis appears to be a main predictive factor in predicting a poor outcome. The ability to tolerate the treatment for long enough was also predictive, as was the presence of factors that increased the likelihood of leakage.37
Conclusion
Normal physiological ageing of the lungs causes a progressive decline in homeostasis which is akin to that seen in COPD.
COPD causes accelerated ageing on a cellular level—increased cellular senescence, increased oxidative stress, stem cell exhaustion and a reduction in endogenous anti ageing molecules.12 As the initial causative factor is oxidative stress targeting this seems to be the next step in targeting future therapies for COPD. Most promising seem to be new glutathione and superoxide dismutase analogues.2
It appears from national statistics that there is a substantial proportion of patients whose COPD remains undiagnosed. Work in the future should look to perhaps improving integrated care pathways and use of spirometry for diagnosis in at risk groups. However, treatment options that offer a mortality benefit are limited. In an elderly population further improving access to pulmonary rehabilitation and also palliative care can help with symptom control and improved quality of life.
There is a higher incidence of pneumonia both secondary to inhaled corticosteroids and otherwise in this population. There is also an increasing proportion of frail elderly patients receiving NIV as a treatment for an acute exacerbation in hospital. Serial national audits report poorer outcomes than documented in randomised controlled trials and higher mortality when compared with patients that did not receive NIV matched by arterial pH.38-40 Are we therefore over-treating our elderly? Further research is needed into the risks and benefits, and impact of high dose inhaled corticosteroids in this group, as well as development of new therapies for COPD.
Jayadev A, The Royal Free Hospital, London
Gill SK, The National Hospital for Neurology and Neurosurgery, University College London
Conflict of interest: none declared
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