COPD Yesterday and Today; Achievements and Challenges Zurab Gurul MD, PhD
The history of COPD The evolution of knowledge concerning COPD and its components emphysema, chronic bronchitis, and asthmatic bronchitis covers 200 years. Some of the earliest references to the description of emphysema include: Bonet s description of voluminous lungs in 1679 (Bonet 1679); Morgagni s (1769) description of 19 cases in which the lungs were turgid, particularly from air; and Baille s illustrations of the emphysematous lung, thought to be that of Samuel Johnson (Baillie 1789). The beginnings of our clinical understanding of the chronic bronchitis component of COPD can be traced to Badham (1814), who used the word catarrh to refer to the chronic cough and mucus hypersecretion that are cardinal symptoms. He described bronchiolitis and chronic bronchitis as disabling disorders
The emphysema component of disease was beautifully described by Laënnec (1821) in his Treatise of diseases of the chest. Laënnec, a clinician, pathologist, and inventor of the stethoscope, did careful dissections of patients that he had studied during life. He recognized that emphysema lungs were hyperinflated and did not empty well. John Hutchinson invented the spirometer in 1846. Hutchinson s instrument only measured vital capacity. It took another 100 years for Tiffeneauto add the concept of timed vital capacity as a measure of airflow, for spirometryto become complete as a diagnostic instrument
In 1944, one of the great teachers of emphysema, Ronald Christie, suggested that The diagnosis should be considered certain when dyspnea on exertion, of insidious onset, not due to bronchospasm, or left ventricular failure, appears in a patient who has some physical signs of emphysema together with chronic bronchitis and asthma. Barach and Bickerman(1956) edited the first comprehensive text book, Pulmonary emphysema, which nicely describes the treatment of the era. These two physicians were early champions of treatment for emphysema. Contributors to this book included Dickerson Richards, Nobel Laureate, who wrote on the pulmonary circulation and cor pulmonale.
Other acronyms that predated the COPD designation were chronic obstructive bronchopulmonary disease, chronic airflow obstruction, chronic obstructive lung disease, nonspecific chronic pulmonary disease, and diffuse obstructive pulmonary syndrome. William Briscoe is believed to be the first person to use the term COPD in discussion at the 9th Aspen Emphysema Conference. This term became established and today we refer to COPD as the designation of this growing health problem (Briscoe and Nash 1965). Today, COPD is a steadily growing global healthcare problem, with increasing morbidity and mortality
COPD Statistics: Worldwide, COPD affects 329 million people or nearly 5% of the population. In 2011, it ranked as the fourth-leading cause of death, killing over 3 million people It resulted in an estimated economic cost of $2.1 trillion in 2010
In the US COPD is the 4th leading cause of death, following lung cancer, heart disease and strokes. In the US, over 120,000 people die a year from COPD. Most of them were smokers. COPD claims the lives of around 30,000 people in the UK. Smoking is the biggest risk factor for developing COPD. Female deaths from COPD have now overtaken male deaths since the year 2000. In the US in 2002, more than 61,000 females died of COPD compared to 59,000 males. Women who smoke are 13 times as likely to die of COPD than women who have never smoked.
Men who smoke are 13 times as likely to die of COPD than men who have never smoked. There are more female sufferers of chronic bronchitis than male sufferers (50% more). Around 55% of emphysema sufferers are male and 45% are female. However, the trends seem to be reversing, as the number of female sufferers is increasing (around 5%) and the number of male sufferers is decreasing (around 10%). Around 600,000 people have been diagnosed with COPD in the UK. Heavy smokers are 30 times as likely to develop COPD.
The relative and absolute risks of death from smoking continue to increase among female smokers The relative risks of death from lung cancer, COPD, ischemic heart disease, any type of stroke, and all causes are now nearly identical for female and male smokers. women who smoke like men die like men.
Other causes of COPD Air pollution People who live in large cities have a higher rate of COPD compared to people who live in rural areas Occupational exposures Intense and prolonged exposure to workplace dusts, chemicals and fumes increase the risk of COPD in both smokers and nonsmokers. coal mining, gold mining, cotton textile industry, occupations involving cadmium and isocyanates, and fumes from welding. The negative effects of dust exposure and cigarette smoke exposure appear to be additive or possibly more than additive
Genetics Currently, the only clearly inherited risk factor is alpha 1-antitrypsin deficiency This risk is particularly high if someone deficient in alpha 1-antitrypsin also smokes It is responsible for about 1-5% of cases and the condition is present in about 3-4 in 10,000 people. Other genetic factors are being investigated
Cystic Fibrosis ( mucous plugging of secretions leading to pneumonia) Bronchiectasis (localized destruction and dilation of bronchial walls from chronic bronchopneumonia) Bronchiolitis obliterans (destruction of bronchioles occurring with ARDS, viral pneumonia, collagen vascular disease, inhalation of NO2, or graft-vs-host disease from bone marrow transplantation) Tracheal stenosis (<5mm, from ischemia of tracheal mucosa following prolonged intubation)
Chronic bronchitis is irritation and inflammation (swelling) of the lining in the bronchial tubes. The irritation causes coughing and an excess amount of mucus in the airways. The swelling makes it difficult to get air in and out of the lungs. The cilia are then unable to help clean mucus from the airways.
Chronic Bronchitis Diagnosis : presence of productive cough on most days of 3 consecutive months occurring for >2 consecutive years Symptoms : frequent pneumonia, bronchospasm, chronic hypoxia, erythrocytosis, pulmonary hipertension, cor pulmonale Patients often tolerate hypoxia without dyspnea Blue Bloater
Emphysema Irreversible destruction of distal airways with loss of septae, usually secondary to smoking
Symptoms: Hyperinflated lungs, cysts, bullae, and destruction of pulmonary capillaries. The patients have less of a tendency to develop cor pulmonale or erythrocytosis Patients are tachypneic in an attempt to maintain a more normal PaO2 Pink Puffer
Diagnostic Methods: The diagnosis of COPD should be considered in anyone over the age of 35 to 40 who has shortness of breath, a chronic cough, sputum production, or frequent winter colds and a history of exposure to risk factors for the disease. Spirometry is used to confirm the diagnosis. Spirometry is fundamental to making a diagnosis of COPD and a confident diagnosis of COPD can only be made with spirometry Spirometry measures the amount of airflow obstruction present and is generally carried out after the use of a bronchodilator,
Two main components are measured to make the diagnosis: the forced expiratory volume in one second (FEV 1 ), and the forced vital capacity (FVC) A diagnosis of airflow obstruction can be made if the FEV1/FVC < 0.7 (i.e. 70%) and FEV1 < 80% predicted. Spirometry is a poor predictor of disability and quality of life in COPD Spirometry predicts prognosis in COPD Spirometry contributes to the assessment of the severity of COPD
Spirometry alone cannot separate asthma from COPD The values for the post-bronchodilator forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) must be compared with the predicted normal values which depend on the individual's age, height and sex International GOLD guidelines note that specific spirometric cut-points (e.g., post-bronchodilator FEV1/FVC ratio < 0.70 or FEV1 < 80,50, or 30% predicted) are used for purposes of simplicity, but that these cut-points have not been clinically validated
COPD is defined by the presence of airflow limitation that is not fully reversible and does not change markedly over several months While post-bronchodilator FEV1/FVC and FEV1 measurements are recommended for the diagnosis and assessment of severity of COPD, the degree of reversibility of airflow limitation (e.g., change in FEV1 after bronchodilator or glucocorticosteroids) is not recommended for diagnosis, or for predicting the response to long-term treatment with bronchodilators or glucocorticosteroids In most cases the diagnosis of COPD is suggested by the combination of the clinical history, signs and baseline spirometry
COPD is heterogeneous disorder, so no single measure can give an adequate assessment of the true severity of the disease in an individual patient. Severity assessment is important because it has implications for therapy and relates to prognosis. Using spirometry alone may underestimate the impact of the disease in some patients and overestimate it in others. Different thresholds for defining mild, moderate and severe airflow obstruction have been recommended. Thresholds of 80%, 50% and 30% are used to define the boundaries as these have implications both for therapy and prognosis and harmonise with the values recommended in the GOLD and the ATS/ERS guidelines. BMI and exercise capacity also reflect the impact of the disease in an individual and predict prognosis
GOLD Criteria for COPD The GOLD classifications are the main method to describe the severity of chronic obstructive pulmonary disease (COPD). GOLD is short for the Global Initiative for Chronic Obstructive Lung Disease, a collaboration between the National Institutes of Health and the World Health Organization. The GOLD guidelines suggest dividing people into four categories based on symptoms assessment and airflow limitation.
GOLD grade Severity FEV 1 % predicted Mild (GOLD 1) 80 Moderate (GOLD 2) 50 79 Severe (GOLD 3) 30 49 Very severe (GOLD 4) <30 or chronic respiratory failure
Beyond office spirometry, complete pulmonary function testing may show increased total lung capacity, functional residual capacity, and residual volume. A substantial loss of lung surface area available for effective oxygen exchange causes diminished carbon monoxide diffusion in the lung (DLCO) in patients with emphysema. This finding may help distinguish COPD from asthma, because patients with asthma typically have normal DLCO values. Arterial blood gas measurement is recommended to rule out significant hypoxemia (partial pressure of oxygen less than 60 mm Hg) or hypercapnia in patients with more severe disease. This is based on FEV1 (less than 40 percent of predicted value), signs of right-sided heart failure, and signs of hypoxemia.
Testing for α1-antitrypsin deficiency is appropriate in selected patients. testing involves measuring circulating α1-antitrypsin levels followed by phenotype testing if levels are abnormal. Patients with severe α1-antitrypsin deficiency usually are of European descent and develop clinical evidence of COPD approximately 10 years earlier than patients who are not α1- antitrypsin deficient. Lung changes associated with severe α1-antitrypsin deficiency usually include lower lung field predilection. α1-antitrypsin deficiency also may cause otherwise unexplained cirrhosis of the liver. Clinical circumstances in which testing for α1-antitrypsin deficiency should be considered include COPD in never-smokers, idiopathic cirrhosis, family history of α1-antitrypsin deficiency, predominantly lower lung emphysema, premature COPD, and refractory asthma at a young age.
Chest X-ray A lateral chest x-ray of a person with emphysema. Note the barrel chest and flat diaphragm.
Chest X-Ray A severe case of bullous emphysema
CT Scan Axial CT image of the lung of a person with endstage bullous emphysema.
Measurement of the Diameters of the Pulmonary Artery and Aorta CT-detected pulmonary artery enlargement (a PA:A ratio of >1) is independently associated with acute exacerbations of COPD and identifies a sub- population at high risk for hospitalization for these events.
COPD and Impaired Left Ventricular Filling Very severe chronic obstructive pulmonary disease causes cor pulmonale with elevated pulmonary vascular resistance and secondary reductions in left ventricular filling, stroke volume, and cardiac output. Moderately severe COPD is associated with significant decrements in left ventricular filling and cardiac output. The magnitude of these associations are greater among participants with a history of smoking, but the associations with percent emphysema are also present among participants who had never smoked.
COPD as a Systemic Disease COPD increasingly is considered a systemic disorder with important non-pulmonary components. Weight loss in patients with COPD may be related to increased circulating levels of inflammatory mediators (e.g., tumor necrosis factor alpha, inflammatory cytokines). Pulmonary cachexia associated with severe COPD also causes profound weight loss, which is a predictor of increased mortality risk independent of lung function. Respiratory and skeletal muscle abnormalities accompany COPD. The respiratory muscles of patients with COPD are chronically overworked and fatigued, whereas the extremity muscles tend to be underworked and atrophied.
Treatment (Bronchodilators) Inhaled bronchodilators are the primary medications used and result in a small overall benefit. There are two major types, β 2 agonists and anticholinergics; both exist in long-acting and short-acting forms. They reduce shortness of breath, wheeze and exercise limitation, resulting in an improved quality of life. It is unclear if they change the progression of the underlying disease. In those with mild disease, short-acting agents are recommended on an as needed basis. In those with more severe disease, long-acting agents are recommended
There are several short-acting β 2 agonists available including salbutamol (Ventolin) and terbutaline. They provide some relief of symptoms for four to six hours. Long-acting β 2 agonists such as salmeterol and formoterol are often used as maintenance therapy. Long-term use appears safe in COPD with adverse effects include shakiness and heart palpitations. When used with inhaled steroids they increase the risk of pneumonia.
There are two main anticholinergics used in COPD, ipratropium and tiotropium. Ipratropium is a short-acting agent while tiotropium is longacting. Tiotropium is associated with a decrease in exacerbations and improved quality of life, and tiotropium provides those benefits better than ipratropium. It does not appear to affect mortality or the over all hospitalization rate. Anticholinergics can cause dry mouth and urinary tract symptoms.they are also associated with increased risk of heart disease and stroke.
Corticosteroids Corticosteroids are usually used in inhaled form but may also be used as tablets to treat and prevent acute exacerbations. While inhaled corticosteroids (ICS) have not shown benefit for people with mild COPD, they decrease acute exacerbations in those with either moderate or severe disease. When used in combination with a LABA they decrease mortality more than either ICS or LABA alone. By themselves they have no effect on overall one-year mortality and are associated with increased rates of pneumonia. It is unclear if they affect the progression of the disease. Long-term treatment with steroid tablets is associated with significant side effects
Other medications Methylxanthine drugs such as aminophylline and theophylline are recommended for use in patients who have acute exacerbations (episodes) of chronic obstructive pulmonary disease, particularly for patients unresponsive to standard therapies. The studies do not give a clear indication of whether there was benefit in terms of reduced symptoms or hospital admissions, but side effects were found to be more common with methylxanthines. Given current evidence, methylxanthines should not be used for acute exacerbations of chronic obstructive pulmonary disease.
Long-term antibiotics, specifically those from the macrolide class such as erythromycin, reduce the frequency of exacerbations in those who have two or more a year. (concerns include that of antibiotic resistance and hearing problems with azithromycin). Mucolytics may be useful in some people who have very thick mucous but are generally not needed. Cough medicines are not recommended.
Oxygen Supplemental oxygen is recommended in those with low oxygen levels at rest (a partial pressure of oxygen of less than 50 55 mmhg or oxygen saturations of less than 88%). In this group of people it decreases the risk of heart failure and death if used 15 hours per day and may improve people's ability to exercise. During acute exacerbations, many require oxygen therapy; the use of high concentrations of oxygen without taking into account a person's oxygen saturations, may lead to increased levels of carbon dioxide and worsened outcomes. In those at high risk of high carbon dioxide levels, oxygen saturations of 88 92% are recommended, while for those without this risk recommended levels are 94-98%.
Lung volume reduction surgery Vanishing lung syndrome, otherwise known as idiopathic giant bullous emphysema. A 41-year-old man with a smoking history of 30 packyears presented with chronic chest pain, dyspnea, and cough.
Preoperative care for the patient with COPD Determine the type of COPD, its severity, and the chronicity of symptoms. Optimize medical management a) Treat any underlying respiratory infections; b) Optimize bronchodilator therapy; c) Facilitate pulmonary toilet; d) Initiate patient participation ( weight loss, incentive spirometry, exercise) e) Smoking cessation ( effective only if >6-8 weeks)
Deleterious effects of smoking: Nicotine causes sympathetic stimulation with tachycardia and has been implicated with impaired wound healing. Carbon monoxide (CO) can also cause: a) Negative inotropy; b) Leftward shift of the O2-Hgb dissociation curve ( The half-life of CO is 4-6 hours, so normalization of CO levels 1% in nonsmokers vs. 6% in smokers occurs within 12 hours following cessation of smoking). Acute discontinuation of smoking has not been shown to be helpful. In fact, it may cause airway irritability and actually lead to to an increased incidence of postop atelectasis, pneumonia, pulmonary dysfunction, and DVT s.
How to assess the pt s COPD? H/P ( focusing on symptoms of cough, dyspnea, exercise tolerance, cyanosis, clubbing, pneumonia, hospitalizations and medications). PE ( Respiratory pattern, RR, use of accessory muscles, signs of RV failure hepatosplenomegaly, edema, JVD) Labs: CBC (erythrocytosis), CXR, EKG (RVH); ABG ( hypoxemia and hypercarbia), and electrolytes ( metabolic alcalosis for hypercarbia).
What is the significance of a increased RR? It depends on the pt s baseline RR and whether he/she has emphysema or chronic bronchitis. A) With chronic emphysema, the RR is faster than with chronic bronchitis due to a preserved drive to maintain normal PaO2 and PaCO2 values. B) With chronic bronchitis, patients are more tolerant of hypercarbia and hypoxemia and tachypnea is often late sign of distress. C) Tachypnea can also be due to pain or anxiety.
Which spirometric studies are most The most basic one is FEV1. helpful? Patients with a FEV1<50% may be at risk for failing extubation or developing postop respiratory complication. For pneumonectomies, a preop FEV1 of 1600 cc is often cited as necessary to achieve a predicted postpneumonectomyfev1 of 800 cc; However, such values depend on body size and are not without exception. As an anestesiologist, I rarely order spirometry, despite the long list of theoretical reasons for doing so.
Why Not? The reasons for ordering FEV1 of FVC cited in textbooks can often be obtained by H/P. To determine the response to bronchodilators, simply ask the patient if he/she were taking bronchodilator and whether they were of any benefit. To assess the severity of disease and predict whether someone can be extubated, one can depend on good H/P. While it is true that patients with preop FEV1<50% predicted are most likely to require postop mechanical ventilation, such predictions depends entirely on the type and course of surgery.
There is no best technique The choice o anesthetic depends on the: a) Type and duration of surgery; b) Preferences of the surgeon,, patient and anesthesiologist; c) Perioperative goals ( extubation, etc.) Is epidural always safe? Even though a motor blockade above T6 does not usually affect TV in normal individuals ( the diaphragm (C3-5) is the major muscle of respiration), it may impair respiration in COPD patients depend on active expiration.
How to ventilate the patient with COPD? Since the pathophysiology of COPD involves increased airway resistance that impedes exhalation, goals are to minimize this resistance and allow adequate gas emptying. a) Slow respiratory rates; b) Minimize peak airway pressures; c) Humidification of gases; d) 100% )2 if hypoxemia (PaO2<60 %) were present; Attempting to achieve normocapnia in a chronic CO2 retainer may cause alkalosis!
How to reduce the chances of postop respiratory complications? Good pain control Adequate Chest physiotherapy and incentive spirometry Bronchodilators should be continued, or if needed, begun Conservative fluid management ( to minimize the chances of pulmonary edema)
Chronic obstructive pulmonary disease is a common disease with a high incidence and a medico-economical impact which should not be underestimated. The extensive comorbidity of COPD patients as well as the impairment of the respiratory system make COPD a key challenge for every physician. Knowledge of the pathogenesis, course and prognosis, and new approaches to therapy have dramatically improved our understanding of this important clinical entity. Early identification and prevention, and adequate treatment of emerging stages of disease promises to change the outcome.