This article summarizes the morbidity and mortality associated with COPD and was created from a presentation given at the 130th AAIM Annual Meeting. The author reviews what most medical directors already know about COPD, but with particular attention paid to the Pulmonary Function Tests dealing with spirometry. Underwriters and medical directors need to understand the three basic measurements of spirometry (FVC, FEV1, and FEF25-75), as well as the significance of the FEV1/FVC ratio, in establishing an applicant as having an obstructive or restrictive impairment.
The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. It is estimated that between 300 and 400 million people globally live with COPD, with particular concern in low- and middle-income countries due to increasing rates of smoking, household- and ambient air pollution and other exposures, coupled with large and ageing populations. Furthermore, the ongoing COVID-19 pandemic highlighted COPD as a condition that predisposes to increased risk of hospitalization and death.1,2
COPD is the 4th-ranked cause of death in the United States, killing more than 120,000 individuals each year and 3 million deaths around the world. It affects more than 5% of the US population and may be associated with significant morbidity and mortality. From an underwriting standpoint, it is estimated that there are almost as many persons with undiagnosed COPD as those carrying this diagnosis. It has been found that most persons seeing a physician for the first time for symptoms of COPD on spirometry are found to have late-moderate to early-severe disease as measured by GOLD spirometry criteria.
In never-smokers, airway lumen at chest CT images was smaller in women than men. In ever-smokers, worsening of lumen size impacted respiratory outcomes more in women than men. With the prevalence of COPD in women fast approaching that in men, women experience greater symptom burden and mortality.3
A key feature of COPD is an accelerated rate of decline in forced expiratory volume in the 1st second (FEV1 – best expressed clinically as FEV1% predicted). Changes in FEV1 after administration of a bronchodilator over a 3-year period were studied in 2163 persons. The mean (±SE) rate of change in FEV1 was a decline of 33±2 ml per year, but with significant variation among persons studied. Thirty-eight percent of persons had an estimated decline in FEV1 of more than 40 ml per year.4 The rate of decline was greater in current smokers, persons with emphysema compared to those without emphysema, and persons with some bronchodilator reversibility (Asthma-COPD overlap, or ACO) compared to those without reversibility.
Although FEV1 is often used to grade the severity of COPD, persons with COPD have systemic manifestations that are not reflected by the FEV1. In an evaluation of 207 persons with COPD, four factors predicted the risk of death in this cohort: the body-mass index (B), the degree of airflow obstruction (O) and dyspnea (D), and exercise capacity (E) measured by the 6-minute-walk test. These variables were used to construct the BODE Index, a multidimensional 10-point scale in which higher scores indicate a higher risk of death. This index was prospectively validated in a cohort of 625 persons, with death from any cause and from respiratory causes as the outcome variables. Persons with higher BODE scores were at higher risk for death; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.32 (95% CI, 1.26-1.42; P<0.001), and the hazard ratio for death from respiratory causes was 1.62 (95% CI, 1.48-1.77; P<0.001). The C statistic for the ability of the BODE Index to predict the risk of death was larger than that for the FEV1 (0.74 vs 0.65). (See Table 1 )
“We do not need to add up the ‘BODE points’ as if we are doing clinical research, but we do need to search the attending physician's statement for each of these characteristics, and then piece them together into a global view of the applicant. If the proposed insured is losing weight, has a reduced FEV1%p, is dyspneic, and is unable to exert himself, then our job is easy,” states Paul Quartararo, MD, Medical Director at New York Life and co-presenter at the 2022 Pulmonary Workshop.
As noted above, decreasing body mass is associated with increasing mortality. The fat-free mass index (FFMI) can identify a subgroup of persons with an increased mortality despite a normal BMI, and the FFMI is a better predictor of disease severity than is BMI alone. Persons with COPD who are obese have more of the phenotype of chronic bronchitis – “blue bloaters,” while emphysema patients are typically more underweight – “pink puffers.” Potentially related to these observations is the observation that obese persons with emphysema often have low muscle mass contributing to worse lung function, exercise tolerance, and muscle strength compared to emphysema persons with comparable BMI and normal muscle mass.7
Structural, mechanical effects of obesity on lung function are known. Accumulation of fat in the mediastinum and abdominal and thoracic cavities causes reduction in lung volume, in functional residual capacity (see “lung volumes” at end of this document), and in the compliance of the lungs and chest wall.
Yet obesity is more than a state of increased BMI. What we've begun to understand is that its impact on the lungs and respiratory health is much more complicated than just a mechanical problem. With obesity, adipose tissue changes not only in quantity but in function, producing proinflammatory cytokines and hormones – such as tumor necrosis factor-alpha (TNF-alpha), leptin, and interleukin-6 – that can have direct deleterious effects on the lung. Associations between lung disease and the metabolic and other disturbances of obesity are most established in asthma research and have taken hold in the realm of sleep-disordered breathing. But as the prevalence of obesity continues to grow, its role in other lung diseases such as chronic obstructive pulmonary disease and, most recently, pulmonary arterial hypertension (PAH), is gaining more attention in academia.8,9
A major red flag for mortality in COPD is hypercapnic respiratory failure, signaled by the progressive rise in an individual's arterial carbon dioxide levels and decrease in arterial pH. This condition is commonly referred to as “chronic hypercapnic respiratory failure” and is usually seen with very low FEV1 levels and carries a significant risk for death within 5 years. If bloodwork is available, the serum bicarbonate will be elevated (to compensate for the [respiratory] acidosis), and on arterial blood gases (ABGs), the pCO2 will be elevated and the pH decreased. Pulmonary arterial hypertension (PAH) is often co-existing in this population and compounds the morbidity and mortality of this population.
COPD itself is an independent risk factor for lung cancer and increases the risk of lung cancer by 6- to 13-fold relative to individuals without COPD. The association of emphysema with lung cancer is stronger than the association of chronic bronchitis with airflow limitation and lung cancer.
Airway hyperresponsiveness (defined as a post-bronchodilator improvement of FEV1 by ≥12% but not improving back to normal as might be seen in asthmatics) affects approximately 25% of persons with COPD (Asthma-COPD overlap, now known as ACO Syndrome) and is associated with more rapid decline in lung function and mortality. Combined data from two large studies (5938 total participants) found that airway hyperresponsiveness was associated with greater respiratory mortality (HR 2.38, 95% CI, 1.38-4.11).10
In a meta-analysis of 18 studies (418,251 patients) looking for significant predictors of mortality in COPD within a 3-24 month span, previous hospitalization for acute exacerbation (HR 1.97; 95% CI 1.32-2.95), hospital readmission within 30 days (HR 5.01; 95% CI 2.16-11063), cardiovascular comorbidity (HR 1.89; 95% CI 1.2501.59), age (HR 1.74; 95% CI 1.3801.59), male sex (HR 1.68, 95% CI 1.38-1.59), and long-term oxygen therapy (HR 1.74; 95% CI 1.10-2.73) were reported.11
Relationship between Copd and Cvd
Cardiovascular diseases (CVDs) are arguably the most important comorbidities in COPD, and their presence is associated with increased all-cause and CVD-related mortality. Indeed, the typical COPD patient is just as likely to die from a cardiovascular disease as they are from a respiratory one.
While smoking remains an important shared risk factor for both diseases, it is becoming more widely accepted that responses to smoking are not the sole reason for the observed association between COPD and CVD. Our perceptions of COPD as a disease have changed. No longer “just a disease of the lungs,” COPD is now described as the pulmonary component of systematic endothelial disease whereby a range of “inflammageing” processes simultaneously affect multiple organs giving rise to a state multimorbidity, without any clear indication as to which disease came first.12
A meta-analysis of observational studies supports more than a two-fold increase in the odds of having any CVD in persons with COPD relative to COPD-free patients [odds ratio (OR) = 2.46; 96% CI; 2.02-3.00; p<0.0001], and the ORs in the range 2-5 for ischemic heart disease, arrhythmias, heart failure, and diseases of the arterial circulation. Additionally, patients with COPD reported hypertension more often (OR 1.33, 95% CI 1.13-1.56; p-0.0007), diabetes (OR 1.36, 95% CI 1.21-1.53; p<0.0001) and ever smoking (OR 4.25, 95% CI 3.23-5.60; p<0.0001).13
A more recent meta-analysis reveals accumulating evidence suggesting a temporal association between COPD exacerbations and acute CV events, likely due to lung hyperinflation, increased hypoxemia and systemic inflammation. In a review of 7 studies examining the risk of CV events 1-3 months after an exacerbation compared for no exacerbations, relative risk (RR) was 1.68 (95% CI, 1.19-2.38) for stroke, RR 2.43 (95% CI, 1.40-4.20) for acute myocardial infarction.14
Cardiovascular Disease (CVD), heart failure and cardiac arrhythmias are among the most observed CVDs seen in persons with COPD. Estimates of the prevalence of ischemic heart disease in people with COPD vary from less than 28% to over 70%, depending on the characteristics of the study population. Heart failure prevalence estimates lie in the range 10%-30%. Prevalence estimates for arrhythmias also exhibit a degree of variability depending on the clinical setting but are typically between 10%-15%. Unadjusted RR estimates of unspecified CVD among patients with COP compared with patients without COPD ranged from 2.1 to 5.0, with this association persisting after adjustment for shared risk factors in most studies.15
Stroke prevalence in community or primary care COPD populations is generally less than 10% but can be as high as 20% in hospital-based cohorts.16
Peripheral arterial disease (PAD) was found in 8.6% of COSYCONET study participants who had a diagnosis of COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.17
Several studies have investigated whether CVDs are more prevalent in certain subtypes of COPD (ie, emphysema, chronic bronchitis, asthma-COPD overlap (ACO Syndrome). What has emerged is that CVD comorbidity is not confined to those with more advanced airflow obstruction but occurs across the entire spectrum of COPD disease severity. There is some suggestion that the prevalence of CVDs (in particular IHD and PAD) may be higher in those with higher body mass index (BMI) and chronic bronchitis.18
Observational studies have also established the reverse association, namely that COPD is common in people presenting with various forms of CVD. In CHF, for example, the prevalence of COPD varies between 13% and 39%; in cases of atrial fibrillation, most estimates lie in the range of 10%-15% with some studies reporting prevalence rates in excess of 20%.19
A study conducted by Franssen et al found airflow limitation in 30.5% of patients attending 15 cardiovascular outpatient clinics in 9 European countries (3103 patients). Of these, 11.3% had mild, 15.8% had moderate, and 3.4% had severe or very severe airflow obstruction. Significantly, more than 70% of those with airflow limitation had not previously had spirometry or been diagnosed with pulmonary disease.20
Attention has focused on acute events, namely myocardial infarction and stroke, for which an increased risk in COPD is now well established. It is generally accepted that having a diagnosis of COPD approximately doubles the mortality risk of an MI (clearly with smoking or history of smoking contributing to this association).21,22
Evidence is accumulating that COPD is linked to increased risks for CVD outcomes other than MI and stroke. The indications are that the magnitude of the increased risk associated with COPD for outcomes such as heart failure, angina and cardiac arrhythmias, as well as diseases of the arterial circulation, is even greater than that for MI and stroke. Curkendall et al estimated an age-adjusted risk ratio for heart failure of 4.5 (95% CI:2.8-6.2) in a Canadian cohort, while Agarwal et al in their longitudinal study of a United States cohort of patients aged 45-64 years found that the incidence of heart failure increased with decreasing FEV1, even after adjustment for age, smoking, and other cardiovascular risk factors.23,24
Although studies have overall failed to find convincing evidence that frequent exacerbators (defined as 2 or more exacerbations in 1 calendar year) are at greater risk for acute CVD outcomes (MI and Stroke) than people who rarely experience an exacerbation of their symptoms, the period immediately after an acute exacerbation of COPD (AECOPD) has been shown to be a period of high risk for such events.25
There are a number of mechanisms that provide a putative link between COPD and CVD, which may be driving CVD risks in COPD. The observation that arterial stiffness is more pronounced in patients with COPD compared in controls matched for age and smoking status has led to the hypothesis that COPD is associated with elastin degradation both in the lung (where it results in emphysema) and in the vasculature – systemic elastin degradation – where it results in increased arterial stiffness. Arterial stiffness is considered a surrogate indicator of coronary, cerebrovascular and PAD and is assessed by measuring aortic pulse wave velocity. This measure is strongly associated with cardiovascular mortality in the general population and is of potential interest as a predictive marker of CVD risk in COPD.28
Patients with COPD are subject to sustained or intermittent hypoxia. Hypoxia is known to induce increased systemic inflammation, oxidative stress, foam cell production and up-regulation of cellular adhesion molecules in endothelial cells, which may contribute to progression of atherosclerosis. Chronic hypoxia also induces pulmonary vascular remodeling (intimal and medial thickening) and pulmonary artery endothelial dysfunction.
Therapies in Copd
Evidence from many clinical trials suggests that inhaled COPD therapies do not pose a significant CVD risk, at least in persons free from cardiovascular comorbidities.29
However, an impressive study from Canada (using UK Clinical Practice Research Datalink) of 180,567 new asthmatic users of β2-agonists (SABA), inhaled corticosteroid (ICS), short-acting muscarinic agonists (SAMA) or long-acting muscarinic agonists (LAMA) were not associated with the risk of MACE (major adverse cardiovascular events) – (SABA vs ICS: HR 1.29 [95% CI 0.96-1.73]; ICS/LABA vs ICS, HR 0.75 [95% CI 0.33-1.73]. In contrast, among COPD patients, new-use of long-acting beta-agonists (LABA) (HR, 2.38 [95% CI 1.04-5.47] and ICS/LABA (HR, 2.08 [95% CI 1.04-4.16] had an increased risk of MACE compared with SAMA users. Among patients with asthma-COPD overlap (ACO syndrome), new prescriptions for SABAs were associated with an increased risk of MACE compared with ICS (HR, 2.57 [95% CI 1.26-5.24]. The authors concluded that initiation of LABA, SABA, or ICS/LABA in COPD or SABA in asthma-COPD overlap was associated with increased risk of MACE, compared with ICS alone.30
A concurring study found that cardiovascular risk (as measured by hospital admission or emergency room attendance for CVD) was increased in new long-acting beta agonist (LABA) or long-acting muscarinic antagonist (LAMA) users OR = 1.31 (CI 95% 1.12-1.52) and OR = 1.14 (CI 95% 1.01-1.28), respectively.31
The SUMMIT trial, which included 16,000 people with moderate COPD at increased risk for or with a history of CVD, was designed to allow stratification to assess cardiac effects of LABA treatment in these groups. Interim results suggest that while use of a LABA either alone or in combination with inhaled corticosteroid may reduce the rate of FEV1p decline, the benefits of therapy appear to be confined to the respiratory system – LABA therapy appears to have no beneficial effect on mortality or a composite CVD outcome.32,-34
Beta-blockers have long been avoided in persons with COPD for fear of worsening bronchospasm. However, in a meta-analysis of 15 retrospective studies involving patients with COPD, those who received beta-blockers had a 28% lower frequency of death and a 38% lower frequency of exacerbation than those who did not receive a beta-blocker.35
These results were questioned in the BLOCK COPD (Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) trial, where patients with COPD without overt cardiovascular disease were given long-acting metoprolol vs placebo. This study was stopped early because of the futility of achieving a salutary outcome for the primary end point. There was no between-group difference in the time until the first exacerbation or in the overall rate of exacerbation. However, among patients who received metoprolol, there was a greater risk of severe exacerbation (leading to hospitalization) and very severe exacerbation (leading to intubation and mechanical ventilation) in patients with more severe COPD. Although the FEV1 was similar in the two groups, there was a greater increase in a score for breathlessness in the metoprolol group, which suggests an adverse effect of the drug on COPD symptoms. This population contrasts with the patients in most observational studies that have shown positive effects of beta-blockers in patients with COPD who had an indication for treatment with a beta-blocker. The patients in the BLOCK COPD trial were also at higher risk for exacerbation and had at least one exacerbation during the preceding year severe enough to require ER visit or hospitalization. Of this population, 40% were also requiring long-term oxygen therapy. The results of this trial should not deter the use of beta-blockers in patients with COPD who have cardiovascular indications, with the caveat that the risk-benefit ratio should be considered in patients with very severe COPD at high risk for severe exacerbation.36,37
Basics of Copd and Spirometry
The Global Initiative for Chronic Obstructive Lung disease (GOLD) defines COPD as follows: “COPD is a common, preventable, and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases and influenced by host factors including abnormal lung development. Significant comorbidities may have an impact on morbidity and mortality.”
Copd Three Major Subtypes
Chronic bronchitis — a clinical diagnosis defined as a chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of chronic cough (eg, bronchiectasis) have been excluded. It may precede or follow development of airflow limitation. Current and former smokers have increased airway mucin concentration compared with never smokers.
Emphysema — a pathological term that describes some of the structural changes sometimes associated with COPD. These changes include abnormal and permanent enlargement of the airspace's distal to the terminal bronchioles that is accompanied by destruction of the airspace walls, without fibrosis visible to the naked eye. Exclusion of obvious fibrosis is intended to distinguish the alveolar destruction due to emphysema from that due to the interstitial pneumonias.
Subtypes of Emphysema
Proximal acinar (also known as centrilobular) emphysema that refers to abnormal dilation or destruction of the respiratory bronchiole, the central portion of the acinus. This is seen in the lung apices associated with cigarette smoking (due to preferential distribution of initially inhaled air to the apices) and more diffusely in coal workers’ pneumoconiosis.
Panacinar emphysema refers to enlargement or destruction of all parts of the acinus. Diffuse panacinar emphysema is most commonly associated with alpha-1-antitrypsin deficiency and is primarily seen in the lung bases corresponding to predominant blood flow to the lung bases (when patients are standing).
Distal acinar (also known as parastatal) emphysema is where the alveolar ducts are predominantly affected. Distal acinar emphysema may occur alone or in combination with proximal acinar and panacinar emphysema. When it occurs alone, the usual association is spontaneous pneumothorax in a young thin and usually tall adult.
Asthma — “a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment” (Global Initiative for Asthma — GINA).
Patients with asthma whose airflow obstruction is completely reversible are not considered to have COPD. Patients with asthma whose airflow obstruction does not remit completely with bronchodilators are considered to have Asthma with COPD, or ACO Syndrome. The etiology and pathogenesis of the COPD in such patients may be different from that of patients with chronic bronchitis or emphysema.
The transition from asthma with complete reversibility either spontaneously or with inhalation of bronchodilators to asthma that fails to show reversibility back to normal is thought to reflect “remodeling,” with a gradual change from an eosinophilic inflammatory cascade to a neutrophilic inflammatory cascade.
Chronic bronchitis and emphysema with airflow obstruction commonly occur together. Some of these patients may also an asthmatic component.
Individuals with asthma may develop a chronic productive cough, and this is unofficially referred to as having “asthmatic bronchitis.”
Smoking and Inhalational Exposure History
The amount and duration of smoking contribute to disease severity although it must be recognizedthatup to 20%of adults with COPD have no smoking history at all. Smoking history is usually reflected as the number of packs of cigarettes per day multiplied by the number of years smoking — “pack-years.” With enough smoking, almost all smokers will develop some measurably reduced lung function.
In one study, the single best variable for predicting which adults will have airflow obstruction on spirometry is a history of more than 40 pack-years of smoking (positive likelihood ratio (LR), 12 [95% CI, 2.7-50]).
However, other data suggest smoking duration may provide stronger risk estimates of COPD than the composite index of pack-years. For the same amount of cigarette smoking, women have a higher risk of COPD than men.
Other types of tobacco smoke, such as from cigar, pipe, water-pipe, and hookah use also confer a risk. Water-pipe or hookah smoke appears to be as harmful or ever more harmful as smoking cigarettes.
Just a word about cigarette smoking and cancer: In 2019, nearly 123,000 US cancer deaths were from cigarette smoking – 30% of all US cancer deaths. Cancers associated with smoking include cancers of the lung and bronchus, oral cavity, pharynx, esophagus, stomach, colon, liver and liver bile duct, pancreas, larynx, cervix, kidney, pelvis, bladder and acute myeloid leukemia.
History of Fume and Dust Exposure
The chronologically taken environmental/occupational history may disclose other important risk factors for COPD, such as exposure to fumes or organic or inorganic dusts. These exposures help to explain the 20% of individuals who die from COPD that never smoked.
Poorly ventilated fires used for cooking and heating, often fueled by coal or biomass, such as wood and dry dung, may be one of the more common causes of COPD in women in developing countries; these fuels are used as the main source of energy in 80% of homes in India and sub-Saharan Africa.
People who live in large cities have a higher rate of COPD compared to people who live in rural areas.
Genetic Predisposition to COPD
While studies have shown an overall “dose-response curve” for smoking and lung function, there appears to be a genetic predisposition to development of COPD in some individuals as some develop severe disease with fewer pack-years while others have minimal to no symptoms despite many pack-years of smoking. Alpha-1-antitrypsin deficiency is the most widely known genetic genotype causing Panacinar (panlobular) emphysema and, significantly, there is IV replacement therapy for this disease. Other genetic markers for development of COPD are evolving.
Symptoms and Pattern of Onset
The 3 cardinal symptoms of COPD are dyspnea, chronic cough, and sputum production. The most common early symptom is exertional dyspnea. Less common symptoms include wheezing and chest tightness.
Approximately 62% of persons with moderate to severe COPD report variability in these symptoms over the course of the day or week-to-week. Mornings are typically the worse time of day.
Most persons with COPD are overweight or obese. Weight loss, usually in emphysema, generally reflects more advanced disease and is associated with a worse prognosis.
Comorbid diseases that may accompany COPD include lung cancer, bronchiectasis, cardiovascular disease, osteoporosis, metabolic syndrome, skeletal muscle weakness, anxiety, depression, and cognitive dysfunction.
Finally, it is important to note that current and former smokers without spirometry evidence of airflow obstruction can have a substantial respiratory symptom and radiographic burden of disease. While such individuals are being actively investigated, the natural history of such individuals has not been fully studied, and there is currently no evidence to guide treatment and prognosis in such individuals.
There are early reports of distal bronchial wall thickness in some users of vaping who report worsening shortness-of-breath (SOB)
Evaluation of Copd
There is no evidence to support the benefit of population-based screening of asymptomatic adults for COPD. The US Preventive Services Task Force (USPSTF) reaffirms its recommendation against screening for chronic obstructive pulmonary disease 2022,38,39 but the Global Initiative for Chronic Obstructive Lung Disease (GOLD) does advocate active case finding among at risk individuals.
No laboratory test is diagnostic for COPD, but certain tests are sometimes obtained to exclude other causes of dyspnea and comorbid diseases. Assessment for anemia is an important step in the evaluation of dyspnea.
Among stable COPD individuals with normal kidney function, an elevated serum bicarbonate may indirectly identify chronic hypercapnia. In the presence of chronic hypercapnia, the serum bicarbonate is typically increased due to a compensatory metabolic alkalosis. Abnormal results should be confirmed with arterial blood gas measurement.
Testing for alpha-2-antitrypsin (ATT) deficiency should be obtained in all symptomatic adults with persistent airflow obstruction on spirometry. Features that are particularly suggestive of ATT deficiency include emphysema in a young individual (eg, age <45 years), emphysema in a nonsmoker or minimal smoker, emphysema characterized by predominantly basilar changes on chest radiograph or chest CT, a family history of emphysema, or a history of childhood liver disease.
Pulmonary Function Tests
PFTs, particularly spirometry, are the cornerstone of the diagnostic evaluation of patients with suspected COPD (and asthma).
When evaluating a patient for possible COPD, spirometry is performed with pre- and post-bronchodilator administration (eg, inhalation of albuterol 400 mcg) to determine whether airflow limitation is present, and whether it is partially or fully reversible.
American Thoracic Society (ATS) recommended criteria for significant reversibility:
An increase of 12% or greater in the FEV1 or FVC and at least by 200 ml following administration of inhaled beta2-agonist medication.
Airflow limitation that is irreversible or only partially reversible with bronchodilator is the characteristic physiologic feature of COPD. Complete reversibility signifies asthma.
The most important values measured during spirometry are:
Forced expiratory volume in one second (FEV1)
Forced vital capacity (FVC)
Forced expiratory flow 25%-75% (FEF25-75)
The ratio of FEV1/FVC is also reported
The classic volume measurement of the “vital capacity” of the lungs by John Hutchinson in 1842 was marketed to London life insurance companies as a “predictor” of mortality.
The FEF25-75%, also called in some spirometry reports as the MMEF (maximal mid-expiratory flow), is useful for two reasons. The greatest weakness of spirometry as a diagnostic test is that it is effort-dependent (on the part of the person being tested and the person doing the test). Effort is most pronounced at the initiation of spirometry (the initial 25% – “blow, blow, blow”) and the final continuation of spirometry (the final 25% – “keeping pushing, keep pushing”). The FEF25-75% removes these two most-effort-portions of the study.
Second, this measurement is the very first measurement to become abnormal in spirometry, giving a “hint of things to come” in smokers undergoing pre-symptomatic spirometry.
Although the VT (Volume-Time) curves continue to be required for disability determination by many states, for practical purposes the FV (Flow-Volume) curves are the visual representation of spirometry in clinical medicine. The reasons for this are two-fold. First, sub-optimal or frankly poor effort are much more easily seen on FV, rather than VT, curves. Secondly, the degree of “cave-in” of the exahational curve is an easy visualization of the degree of spirometric abnormality, as seen in the figure above.
GOLD Criteria for COPD
FEV1/FVC ratio <70% defines a person as having COPD. FEV1% of predicted (FEV1%p) defines severity of COPD with the following stages:
Mild Stage I FEV1%p ≥80%
Moderate Stage II FEV1%p 50% - 79%
Severe Stage III FEV1%p 30% - 49%
Very Severe Stage IV FEV1%p <30%
There are only 3 diagnoses in spirometry:
When “Restriction” is the spirometric diagnosis, then suboptimal or poor effort may be the cause and further testing is always indicated. Normally, measurements of lung volume and lung diffusion is recommended as follow-up measurements to a spirometry read as “restriction.”
Lung volume measurement is most commonly done via body plethysmography, done in a large plexiglass booth, with measurement of the Functional Reserve Capacity (FRC), and then addition of the Inspiratory Capacity (IC) to arrive at the Total Lung Capacity (TLC). When reading lung volume studies, keep in mind that FRC%p is measured; TLC%p depends on adding the maximal inspiratory capacity (IC%p) to the FRC%p, which may introduce suboptimal effort on the maximal inspiration phase.
Lung diffusion (DLCO) is done by the inhalation of a tiny amount of carbon monoxide with a 10-second breath-hold, and then measuring exhalation of the carbon monoxide over the subsequent several minutes. Decreased DLCO correlates with decreases in alveolar-capillary volume, such as emphysema or interstitial lung disease. Falsely low DLCO may be seen in anemic persons, or if the person has recently smoked – the carboxyhemoglobin (COHb) level of 1% results in a proportionate 1% decrease in the measured DLCO.
PFT reports commonly include the term DLCO/VA. This has been misinterpreted as a correction factor for low lung volume, which leads to a misinterpretation of DLCO results. DLCO/VA (also known as KCO) reflects alveolar CO uptake efficiency at a given lung volume. I have recommended to medical directors and underwriters to ignore this measurement, as it generally reflects certain clinical situations (incomplete lung expansion, pneumonectomy) that can be readily detected in the medical record and can otherwise lead to erroneous assessment.
The combination of these findings may lead to the following diagnoses:
Decreased TLC but normal DLCO → extra-thoracic (obesity, pleural effusion or thickening, or kyphoscoliosis) or neuromuscular diseases
Decreased TLC with decreased DLCO → Interstitial Lung Disease or Fibrosis
Normal TLC with decreased DLCO → Pulmonary Vascular Disease (Pulmonary Hypertension or pulmonary embolism) (Figure 6)