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Chronic obstructive pulmonary disease (COPD) refers to a disease state defined by airflow obstruction that is not fully reversible even after administration of short acting bronchodilators such as salbutamol. (1)The airflow obstruction is usually progressive and is linked with an abnormal inflammatory response to noxious particles or gases. (2) A range of pathologies such as chronic bronchitis, emphysema, bronchiectasis or combination of these may be present in a person suffering from COPD as shown in the following diagram. In addition, bronchodilator reversibility may also be seen which may lead us towards the simultaneous diagnosis of asthma.(1)
Fixed airflow obstruction
Reversibility with short acting bronchodilator
Figure 1: Overlap of conditions seen in COPD (1)
COPD results in a reduction in the ratio of forced expiratory volume in one second (FEV1) to forced vital capacity, such that FEV1/FVC < 0.7 (3) Some of the symptoms of COPD include persistent cough, sputum production, dyspnoea (shortness of breath) . (4) .In addition to the pulmonary symptoms, several systemic conditions such as cardiovascular disease, diabetes, osteoporosis and depression may also be observed in people suffering from COPD. (1)Therefore, COPD is not just a disease but is a syndrome whose effects are not limited just to the lungs. It is important to consider during diagnosis that COPD is more than just a problem with airway obstruction.
Currently around 900,000 people are diagnosed with COPD, but the numbers are expected to be higher. This is because many smokers do not consult their doctors often believing that their symptoms are a result of a 'smoker's cough'. (4) Also partly because it is clinically silent until the disease is well advanced (5)
The British Thoracic Society guidelines recommend that anyone exhibiting the symptoms of COPD should be diagnosed using spirometry to ascertain the presence of airflow limitation. (6) However, the prevalence estimates of COPD differ largely depending on the spirometric criteria used for airway obstruction such as FEV1/FVC fixed ratio < 70% versus lower limit of normal . Meta analysis of epidemiological investigations based on spirometry shows the COPD prevalence to be 8-9%. However, the prevalence of COPD diagnosed by the physicians is only about 1.5% , which is a lot lower than suggested by population based spirometric surveys. Therefore, there is currently an issue of underdiagnosis of COPD in primary care setting and potentially many individuals are not receiving the treatment they require. (7)
Structural and functional changes in the lungs of an individual with COPD:
The innate and adaptive inflammatory response to toxic particles and gases, as result of tobacco smoking is associated with the pathogenesis of COPD. The infiltration of immune cells into the lung tissue is a part of the tissue repair and remodeling process which is caused by the chemical insult to the lung tissue in minority of the smokers. As a result of this process the bronchial mucus glands are enlarged, and the walls of the conducting airways are thickened which narrows their lumen. Although inflammatory process occurs in all the smokers, it does not affect the lung function in majority of the smokers. It is only in the small minority that the inflammatory process is amplified leading to tissue remodeling and hence lesion of the lungs associated with chronic bronchitis and emphysema. (8)
Emphysema is defined as a condition which is characterized by permanent and abnormal enlargement of the alveoli, followed by destruction of their walls without obvious fibrosis. The destruction of alveolar walls is mediated by CD8 T lymphocytes that lead to reduction in elastic recoil which is the driving pressure for flow rate of air out of the lungs. Therefore, emphysema will lead to decreased expiratory airflow by reducing the elastic recoil.(9)
A person is diagonosed with chronic bronchitis if the symptoms of chronic cough and sputum production were seen on most days of the month for at least three months in two consecutive years without any other underlying explanation. (8)
Analysis of sputum of smokers with COPD shows that interleukin-10 (IL 10) which reduces inflammatory response is decreased. On the other hand interleukin-8 (IL-8) which recruits neutrophils are increased. These neutrophils may contribute to increased secretory function of the mucous glands. (9). The increased production of mucus can lead to obstruction of small airways characteristic chronic bronchitis.
The presence of those symptoms does not indicate that the disease will progress to become COPD. This is shown by longitudinal studies of people who had normal lung function despite having the symptoms of chronic bronchitis. However, in individuals with severe airflow limitation presence of chronic bronchitis leads to more rapid decline in lung function.(8,10)
This is also supported by observations made by Fletcher and his associates. They found that majority of subjects who developed air flow limitation did not have chronic bronchitis. They also found that only 15-25% of smokers developed air flow limitation. (8,11)
The flow of air in and out of the lungs is determined by the product of resistance to flow in conducting airways and the elastic force (compliance) of the gas exchange surface (alveoli) that must be overcome. The product of resistance (R) and compliance (C) is defined as the time constant (RC) of the lung as their units simply to time. In normal individuals lung compliance remains constant even though the breathing frequencies are varied. This is because time constants in different region of the lungs are evenly distributed. However, in person with COPD the time constants become longer in regions which are affected by small airway obstruction and/or destruction caused by emphysema. This causes compliance to become frequency dependent. (8, 12)
As COPD become s more severe time required to empty the lungs increases. This is indicated by the measurements of FEV1 and FEV1/FVC which reflects the distribution of time constant within the lung during forced expiration. The increase in time to expire air leads to hyperinflation of the lung as the stimulus to inspire the next breath arrives before the lung has returned to the previous resting level of inflation between breaths. This hyperinflation of lung occurs first at exercise and later at rest, which is the major cause of symptoms in COPD. (8)
Diagnosis of COPD:
The British Thoracic Society guidelines recommend that diagnosis of COPD must be considered in patients aged 35 years who smoke or have smoked, and have chronic symptoms of breathlessness, cough and sputum. This diagnosis is confirmed by using spirometry to demonstrate airflow obstruction.(6)The following diagram demonstrates that smoking accelerates the normal age related decline in lung function.
Figure 2: Normal age related decline in lung function (8)
It also shows that despite the irreversible structural changes produced by tobacco smoke, the decline in lung function returns to normal rate if the patient gives up smoking. Therefore, if COPD is detected early smoking cessation advice could be targeted, which may prevent the progression of the fatal disease. (6)
Spirometry is a method of assessing lung function by measuring the rate at which the lung changes volume during forced breathing maneuvers. It begins with the patient inhaling fully followed by forced exhalation. Exhalation is continued as long as possible or until the plateau for exhalation is reached. The volumes are then recorded on a graph. (13).
Spirometry is a reliable method of differentiating between obstructive conditions such as asthma and COPD, and restrictive diseases such as fibrotic lung disease. Spirometry is also the most effective way of determining the severity of COPD. (6)
Spirometry can also be used to assessing progression of other diseases such as cystic fibrosis and congestive heart failure. It can also be used to assess risk associated with thoracic surgeries such as lobectomy and organ transplantation. (13)
Spirometry gives following three important measures
FEV1 which is the volume of air that the patient is able to exhale in the first second of forced expiration.
FVC which is the total volume of air that the patient can forcibly exhale in one breath
FEV1/FVC which is expressed as a percentage.
Basic spirometry allows us to produce graph shown in figure 3, which shows Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC) in a normal subject and in a person with an obstructive airway. COPD can be diagnosed only if FEV1 < 80% predicted and FEV1/FVC<0.7 (70%). The extent of FEV1 reduction indicates the severity of airflow obstruction in COPD.(6)
Figure 3: FEV1 and FVC in a normal individual and a COPD patient (6)
Many electronic spirometers can measure expiratory flow plotted against the volume of air exhaled. This resulting trace is called a flow volume curve. The overall shape of the curve is helpful for detecting airflow obstruction at an early stage. Following curve is a normal flow volume curve indicating a rapid rise in the expiratory flow which is followed by a steady decline until the air is exhaled. (6)
Figure 4: Normal flow volume curve (6)
In a patient with obstructive airways disease, the peak expiratory flow (PEF) is reduced and the fall in airflow to complete exhalation follows a distinctive dipping curve.
Figure 5: Flow volume curve of an individual with obstructive airway disease (6)
Definitions of the severity of COPD
The NICE COPD guideline defines mild airflow obstruction as FEV1 between 50-80%, moderate airflow obstruction as FEV1 between 30-49% and severe airflow obstruction as FEV1<30% predicted.
The assessment of severity based on FEV1 is important as it can guide pharmacotherapy. It has also been associated with COPD outcomes such as resolution of acute exacerbations and mortality. In addition, it can also provide prognostic information. (14)
Importance of accurate diagnosis of COPD
Drugs which are used to treat COPD such as inhaled corticosteroids have been associated with decreased bone density and increased risk of pneumonia. The use of anticholinergrics in COPD has also been shown to increase risk of cardiovascular events. (14). Therefore, it is important that an accurate diagnosis is made not only to avoid unnecessary risks and costs from the treatment of people without COPD, but also to provide appropriate treatment to the people who actually have COPD.
Evaluation of spirometry in the diagonis of COPD
Factors affecting the accuracy of spirometry
The most common reason for inconsistent readings is patient technique. Factors such as inadequate or incomplete inhalation, lack of blast effort during exhalation and some exhalation through the nose can lead to inaccurate readings. (6)
For example patient's inability to produce maximum exhalation may lead to an underestimation of forced vital capacity (FVC) and occasionally to an underestimation of FEV1. (15) Underestimation of FVC can result in apparent increase in FEV1/FVC ratio, which could potentially label someone with airway limitation as having normal lung function. This may result in the patient not having the treatment they need. On the other hand, underestimation of FEV1 may lead to apparent decrease in FEV1/FVC ratio, which may label a normal person as having the problem of airway limitation. (15) This may expose the patients to unnecessary treatment. Therefore, it is recommended that spirometry is repeated to verify the status of patients with positive test results to reduce false positive outcomes. (15)
In addition, there are quality control aspects for the technicians too which can affect the accuracy of the readings. It is recommended that spirometers must be kept clean, and accuracy checked regularly according to the manufacturer's recommendations. A large volume synringe can be used to calibrate spirometers and to check their accuracy. (6)
Before interpreting the results of spirometry it is important to know whether the tests were performed with satisfactory standards. We should use the data with caution where accepted standards have not been met. Several errors are commonly made when spirometry is used to record data. Patients may fail to start from the true total lung capacity which will give lower FEV1 and FVC readings. If the patient fails to continue to true end of expiration FVC will be low, and it will lead to false increase in FEV1/FVC ratio. Mouth leak also means that peak expiratory flow, FEV1 and FVC will be low. (16)
The predicted values for lung function results must take into account the type of equipment used (17).This is because equipments such as volume accumulating spirometers may have an error in FEV1 measurements (15)eighteen. It is important to consider that single percentage predicated value is not the correct way of determining whether the result is abnormal. This is because the cut off values for abnormality will be different depending on the age, gender and height of the subjects. (16)
Variation of prevalence estimates with different spirometry criteria
Currently there is a lack of consensus about the definition of COPD. (ref10) "The BTS and NICE guidelines define airway obstruction using the fixed ratio of 0.70 and FEV1 below 80% predicated, while GOLD and ATS/ERS COPD guidelines only use the 0.70 fixed ratio (FEV1 can be in normal range)".(19)
The GOLD and ATS guidelines recommend use of spirometry in the accurate diagnosis of COPD. However, the prevalence estimates of COPD using spirometry can vary by two fold or more depending on the definition used to classily mild disease. (20,21,22)
FEV1/FVC fixed ratio has been shown to vary according to the age, weight and gender of the population.(16) nineteen. For example, FEC1/FVC decreases with age even though an individual is healthy and a non smoker . Hence, using FEV1/FVC < 0.7 as a cut off result in wrong diagnoses of normal individuals. The fixed ratio approach appears to overestimate COPD in older individuals aged over 40 and underestimate it in young adults.(20,23,24). Therefore, current ATS/ERS guideline strongly recommend the use of a cut off value for the FEV1/FVC ratio set at the fifth percentile of the normal distribution, rather than at a fixed value of 0.7, in order to reduce number of false positive diagnoses. (5) The prevalence estimates using the fixed ratio criteria (GOLD stage 1 and higher) were significantly higher than for LLN criterion. The added requirement of an FEV1< 80% and FEV1/FVC ratio below LLN were 1-3 percentage points lower than estimates for GOLD stages 2-4. Therefore, use of FEV1/FVC<LLN criterion instead of the FEV1/FVC <0.7 should minimize the known age biases and also better reflect clinically significant airflow limitation. (20)
Chronic obstructive pulmonary disease (COPD) is a spectrum of disorders which include chronic bronchitis and emphysema. It is also one of the major causes of mortality. An early diagnosis of COPD is especially beneficial to the patients who have developed their symptoms due to tobacco smoking, as smoking cessation allows rate of decline in lung function to return to that of a non smoker. (6) However, in England and Wales, there is currently an issue of under diagnosis of COPD.(19)
The current GOLD and ATS guidelines recommend the use of spirometry in the diagnosis of COPD. However, there are issues with the reliability of spirometry as the readings can be inconsistent mainly due to inability of patients to do the test correctly. Therefore, before interpreting the data it is important to ensure that the tests have been carried out with satisfactory standards. (16)
It is logical to assume that a person with COPD will make a transition from normal spirometry to clinically relevant airway obstruction. However, only a small proportion of people with abnormal spirometry results will ever develop COPD, regardless of whether or they smoke. In addition, retrospective analysis of the cardiovascular health study (CHS) show that very few people whose FEV1/FVC indicated that they fall in arbitrary GOLD stage I have actually developed COPD.(25)
It is found that the prevalence rates of COPD vary depending on the spirometry criteria. The fixed FEV1/FVC ratio varies according to age, sex, and weight of an individual. It is important to take this into consideration while interpreting the data to reduce false positives.The fixed FEV1/FVC ratio approach appears to overestimate COPD in older individuals aged over 40 and underestimate it in young adults. In addition, people who fall in the category of GOLD stage I may not necessarily represent people with significant airflow limitation.Therefore, it has been suggested that use of FEV1/FVC<LLN criterion instead should minimize the known age biases and also better reflect clinically significant airflow limitation. (20)