Chronic Obstructive Pulmonary Disease Updated Guidelines and Newer Therapies Heba Ismail, MD Assistant clinical Professor Division of Pulmonary and Critical Care Medicine University of California, Irvine Medical Center E-mail, ismailh@uci.edu Disclosure None Definition The international Global initiative on Chronic Obstructive Lung Disease (GOLD), (WHO/NIH 2009) defines COPD as: ◦ A preventable and treatable disease with some significant extra-pulmonary effects that may contribute to the severity in individual patients. ◦ The pulmonary component is characterized by airflow limitation that is not fully reversible. ◦ The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. Definition This definition no longer describes emphysema, or chronic bronchitis. ◦ COPD is much more a small airways (< 2 mm) disease, pathologically a chronic bronchiolitis caused predominantly by prolonged exposure to tobacco smoke. Destructive alveolar wall rupture occurs from an imbalance between elastases and anti-elastases, and prolonged activation of inflammatory cells causing regional elastin damage with alveolar emphysema. Loss of lung elastic recoil is the key pathophysiological finding, and occurs with emphysema perhaps before loss of alveolar wall and surface area measurable by carbon monoxide diffusing capacity (DLco). COPD and Chronic Bronchitis Chronic bronchitis per se is a smoking related disease of large airways that often resolves after smoking cessation. Patients with COPD who suffer from chronic bronchitis generally show: ◦ Faster functional decline ◦ More exacerbations ◦ Greater morbidity and mortality A greater percentage of smokers with chronic cough can have COPD as compared with smokers without symptoms when functionally reassessed after 8 years. Chronic bronchitis can be considered as both a risk factor for COPD, and a worse prognostic factor in the presence of COPD. Pathology Pathological changes of COPD are found in: ◦ Airways ◦ Lung Parenchyma ◦ Pulmonary Vasculature Pathological changes include: ◦ Chronic Inflammation ◦ Structural changes Pathogenesis Pathogenesis Oxidative Stress Protease-Antiprotease Imbalance Inflammatory cells Inflammatory Mediators Pathophysiology Pathologically, COPD is characterized by two distinct and frequently coexisting aspects: ◦ Small airway abnormalities --- will contribute to airflow limitation by narrowing and obliterating the lumen and by actively constricting the airways, therefore increasing the resistance---decreased FEV1 ◦ Parenchymal destruction (or emphysema)--- airflow limitation and decreased gas transfer Pathophysiology Collapse of small airways during expiration lead to further static hyperinflation. These early changes are not detectable by simple pulmonary function tests (PFT) Reliance on the FEV1/FVC < 0.70 and FEV1 % of predicted remains the current state of the art in COPD screening and staging. A normal DLco does not rule out COPD. Pathophysiology Airflow limitation and Air Trapping Gas Exchange Abnormalities Mucus Hypersecretion Pulmonary Hypertension Systemic Features COPD No blood test, imaging study, or lung function can completely describe impairment from COPD. The BODE Index is a valuable tool Predicting survival in clinical research Assessing disease burden and impairment utilizing Body mass index (BMI) ◦ FEV1 expressed as % of predicted ◦ Severity of dyspnea (the cardinal symptom of COPD) ◦ Exercise capacity or 6-minute walk distance (6MWD) Epidemiology The prevalence of COPD varies by country It is generally linked to the prevalence of tobacco smoking There is also a link to air pollution from the burning of wood and other biomass fuels Worldwide, COPD is one of the leading cause of morbidity and mortality COPD is the 4th leading cause of mortality in the USA, and is also the only one of the top five leading causes of death that is continuing to rise, doubling from 1970 to 2002 It is projected that COPD will become the third leading cause of death worldwide by 2020 COPD deaths among women in the USA have been rapidly rising since the 1970s and have exceeded male COPD deaths since 2000 Epidemiology COPD presents an increasing social and economic burden. COPD patients incur health care costs associated with frequent clinic visits, urgent care visits, and hospitalizations. Home medical therapies, including oxygen therapy, visiting nursing services, and rehabilitation add to the cost . The health-care expenditure for each COPD patient cost on average $6,000 annually. In 2002, the estimated USA direct medical cost of COPD was $18 billion while indirect costs including lost wages and decreased productivity were estimated at $14.1 billion. COPD phenotypes Asthma-COPD overlap syndrome Exacerbators Emphysema-Hyperinflation ◦ Chronic Bronchitis can accompany any of the three phenotypes Proportional Venn diagram presenting the different phenotypes within the Wellington Respiratory Survey study population. The large black rectangle represents the full study group. The clear circles within each coloured area represent the proportion of subjects with COPD (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7). The isolated clear circle represents subjects with COPD who did not have an additional defined phenotype of asthma, chronic bronchitis or emphysema. (Reproduced with permission from Marsh SE, Travers J, Weatherall M et al. Proportional classifications of COPD phenotypes. Thorax 2008; 63: 761-767.) COPD Classification GOLD has classified COPD into four stages based on spirometric values and thus on severity of airflow obstruction (Table 1) . Table 1 Classification of COPD COPD, Management The focus of COPD treatment should be ◦ ◦ ◦ ◦ ◦ Relief of symptoms Improving exercise tolerance and overall health status Prevention and timely treatment of exacerbations Preventing disease progression Reducing mortality . COPD Management Non pharmacotherapy Pharmacotherapy Surgery Minimally Invasive Surgery Smoking Cessation The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines emphasize that smoking cessation is, “the single most effective and cost-effective way to reduce exposure to COPD risk factors”. Pulmonary Rehabilitation According to the ATS statement on pulmonary rehabilitation, it is defined as a ◦ “Multidisciplinary program of care for patients with chronic respiratory impairment that is individually tailored and designed to optimize physical and social performance and autonomy” ◦ Pulmonary rehabilitation improves quality of life, by improving exercise tolerance, and dyspnea. ◦ Pulmonary rehabilitation was found to increase peak workload by 18%, and peak oxygen consumption by 11%. Pulmonary rehabilitation should be considered for COPD patients with reduced exercise tolerance and limitation of their daily activities secondary to their disease. COPD, Pharmacotherapy ◦ Pharmacologic therapy is able to significantly improve the quality of life and reduce the frequency of exacerbations BUT ◦ Unable to halt the annual decline in FEV1 or unequivocally reduce mortality, with the important exception of oxygen therapy where indicated. Oxygen Therapy Long-term oxygen therapy (more than 15 hours a day) has been shown to ◦ Improve survival ◦ Exercise tolerance ◦ Pulmonary hemodynamics including pulmonary artery pressure, lung mechanics and mental status. Indications of long term oxygen therapy include: ◦ PaO2 at or below 55 mmHg or/ SaO2 of less than or equal to 88% ◦ PaO2 between 55 mmHg and 60 mmHg, SaO2 of 89% if there is evidence of pulmonary hypertension, peripheral edema suggesting congestive heart failure or polycythemia. Pharmacotherapy Bronchodilators ◦ They do not alter the decline in lung function. ◦ They decrease expiratory trapped air volume and reduce dynamic hyperinflation during exercise as well as at rest. ◦ They are prescribed in both short- and longacting forms for immediate (rescue) and sustained relief, respectively. Pharmacotherapy Long-acting bronchodilators are recommended for patients with moderate to severe COPD. In the largest trial of a Salmeterol, long-acting beta-2 agonist (LABA), Toward a Revolution in COPD Health (TORCH), patients with a mean forced expiratory volume in one second (FEV1) of 44% of predicted were randomly assigned to one of four treatment arms for 3 years: ◦ ◦ ◦ ◦ Salmeterol alone (50 mcg twice daily) Fluticasone alone (500 mcg twice daily) Combination of both Placebo Pharmacotherapy The Salmeterol alone and combination arms each revealed improved lung function, health-related quality of life, and reduced exacerbation rates compared to the placebo arm. No statistically significant mortality reduction was seen. However, the combination of Fluticasone and Salmeterol showed a trend towards a significant reduction of all-cause mortality by 17.5% in 3 years compared to placebo. TORCH Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Peter M.A. Calverley, M.D., Julie A. Anderson, M.A., Bartolome Celli, M.D., Gary T. Ferguson, M.D., Christine Jenkins, M.D., Paul W. Jones, M.D., Julie C. Yates, B.S., and Jørgen Vestbo, M.D. for the TORCH investigators N Engl J Med 2007; 356:775-789February 22, 2007DOI: 10.1056/NEJMoa06307 Pharmacotherapy Tiotropium, was assessed in a randomized trial Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT). Among patients with moderate (45%) and severe (44%) COPD, Tiotropium or placebo was added to ongoing care, that is, inhaled corticosteroids, long-acting beta-2 agonists, and/or theophylline, for a duration of 4 years. Tiotropium significantly reduced the risk of exacerbations and associated hospitalizations and respiratory failure when added to usual care. There was no difference in the annual rate of decline of FEV1 or mortality between the two groups . An intention-to-treat analysis that assessed mortality after 4 years, the use of Tiotropium reduced all cause mortality by 13% (HR = 0.87, 95% CI 0.76–0.99, ). Pharmacotherapy The combination of bronchodilators of different classes and durations may provide an improved effect with fewer side effects . For example, the combination of a LABA and an anticholinergic (Tiotropium) showed an improved FEV1 by the end of a 12-week trial . In another study, the use of a short acting beta-agonist plus an anticholinergic showed a greater and longer-lasting FEV1 improvement when compared to each drug alone . No clear data are available as to which long-acting bronchodilator combination provides the best relief. Current guidelines recommend weighing the risks and benefits of each for the individual patient . Pharmacotherapy Although pulmonary inflammation plays an important role in the pathophysiology of the disease, inhaled corticosteroids (ICS) have not definitively been shown to decrease the rate of lung function decline or change COPD morbidity per se. However, the addition of an ICS may prove beneficial for some patients. Pharmacotherapy In the TORCH study, the combination of a LABA plus ICS resulted in a decrease in the number of exacerbations along with sustained benefits in health status and sustained improvement in FEV1 when compared to Placebo, Salmeterol alone and Fluticasone alone . This combination is typically reserved for patients with GOLD stages 3 and 4 with recurrent exacerbations, or for those who have baseline eosinophilic component of their disease or associated asthma. Pharmacotherapy A recent meta-analysis readdressed the possibility of a favorable effect on mortality when combining ICS and bronchodilators in COPD. Use of an ICS combined with LABA demonstrated a 20% reduction in total mortality, with a mortality risk ratio of 0.80 (95% CI, 0.69–0.94). However, use of a LABA or Tiotropium alone did not decrease the mortality rate . There is also concern that the use of high dose ICS in patients with COPD may be associated with an increased risk of pneumonia. Therapy at Each Stage of COPD I: Mild II: Moderate III: Severe IV: Very Severe FEV1/FVC < 70% • FEV1/FVC < 70% • FEV1/FVC < 70% • FEV1 > 80% predicted • 50% < FEV1 < 80% predicted • FEV1 < 30% predicted • FEV1/FVC < 70% or FEV < 50% 1 predicted plus • 30% < FEV1 < chronic 50% predicted respiratory failure Active reduction of risk factor(s); influenza vaccination Add short-acting bronchodilator (when needed) Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation Add inhaled glucocorticosteroids if repeated exacerbations Add long term oxygen if chronic respiratory failure. Consider surgical treatments Novel Pharmacotherapy Phosphodiesterase (PDE) Inhibitors N-Acetylcysteine (NAC) TNFα Inhibitors-Infliximab ABX-IL8 Anti-leukotriene Drugs Prophylactic Use of Macrolides Vitamin D Novel Pharmacotherapy Inflammatory cells such as neutrophils, CD8 lymphocytes, and macrophages, express predominantly phosphodiesterase (PDE) type 4. PDE type 4 hydrolyzes cyclic adenosine monophosphate (cAMP) in inflammatory cells. By inhibiting PDE type 4, intracellular cAMP concentrations increase which leads to activation of protein kinase A, phosphorylation and inactivation of target transcription factors, which ultimately result in reduction of cellular inflammatory activity. While theophylline is a nonspecific PDE inhibitor (thus with a large side-effect profile including diarrhea, seizures and cardiac arrhythmias), several new drugs have been tested that target PDE type 4 specifically, notably Cilomilast and Roflumilast PDE-4 PDE-4 Inhibitors The safety and efficacy of Cilomilast (15 mg twice daily) was evaluated in ◦ A double-blind placebo-controlled study ◦ Significant increase in FEV1 as well as fewer exacerbations over a 24week period. Gastrointestinal side effects (nausea and diarrhea) were greater in the first 3 weeks of the study in the treatment arm. Cilomilast has been evaluated in three additional multicenter, randomized, placebo-controlled phase III trials. ◦ The change of FEV1 (from 30–40 mL) compared to placebo was significant in only two of the four studies. Overall, these studies did not show as large of improvements in FEV1 as was expected based on phase II trials. PDE-4 Inhibitors Roflumilast is a more potent PDE type 4 inhibitor compared to Cilomilast . In a phase III multicenter placebo-controlled trial, 1411 patients were randomly assigned to receive Roflumilast 250 mcg, Roflumilast 500 mcg, or placebo daily for 24 weeks. Post-bronchodilator FEV1 at the end of treatment significantly improved for both groups of Roflumilast when compared to placebo (74 mL with the lower dose and 97 mL with the higher dose medication). Both groups suffered fewer mild exacerbations while moderate to severe exacerbations were unchanged. The most common side effects were also diarrhea and nausea. PDE-4 Inhibitors Two randomized clinical trials on the use of Roflumilast compared to placebo were published in 2009. Patients in these studies had COPD with severe airflow obstruction, documented cough and sputum production, and a history of frequent COPD exacerbations in the past year. In pooled analysis, the pre-bronchodilator FEV1 increased by 48 mL among those with the treatment drug, a statistically significant improvement compared to placebo. PDE-4 Inhibitors Moderate to severe exacerbations were also significantly less in the treatment arm. When compared to placebo, the addition of Roflumilast to Salmeterol was associated with a 49 mL prebronchodilator FEV1 increase, and an 80 mL increase when added to Tiotropium Side effects such as nausea, diarrhea and weight loss contributed to greater patient withdrawal Surgery and Minimally Invasive (Non-Surgical) Approaches Bullectomy Lung Volume Reduction Surgery Minimally Invasive approaches ◦ ◦ ◦ ◦ Endobronchial Blockers Bronchial Fenestration and Airways Bypass Endobronchial Valves Biological Lung Volume Reduction (Sealants) Surgery for COPD Bullectomy Bullectomy appears to be of benefit in highly selected patients resulting in short-term improvements in airflow obstruction, lung volumes, hypoxaemia and hypercapnia, exercise capacity, dyspnea, and health-related quality of life. Surgical mortality ranges from 0-22.5% Long-term follow-up data are more limited with 1/3-1/2 of patients maintaining benefits for ~5 yrs Patient selection ◦ most investigators have attempted to identify optimal surgical candidates on the basis of pulmonary function and radiographic features Bullectomy Patient Selection Lung Volume Reduction Surgery LVRS LVRS, NETT Methods ◦ A total of 1218 patients with severe emphysema underwent pulmonary rehabilitation and were randomly assigned to undergo lung-volume– reduction surgery or to receive continued medical treatment LVRS, NETT LVRS, NETT Results ◦ Overall mortality was 0.11 death per person-year in both treatment groups. ◦ After 24 months, exercise capacity had improved by more than 10 W in 15 percent of the patients in the surgery group, as compared with 3 percent of patients in the medical-therapy group (P<0.001). ◦ With the exclusion of a subgroup of 140 patients at high risk for death from surgery according to an interim analysis, overall mortality in the surgery group was 0.09 death per person-year, as compared with 0.10 death per person-year in the medical-therapy group (risk ratio, 0.89; P=0.31). ◦ Exercise capacity after 24 months had improved by more than 10 W in 16 percent of patients in the surgery group, as compared with 3 percent of patients in the medical-therapy group (P<0.001). LVRS, NETT ◦ Among patients with predominantly upper-lobe emphysema and low exercise capacity, mortality was lower in the surgery group than in the medicaltherapy group (risk ratio for death, 0.47; P=0.005). ◦ Among patients with non–upper-lobe emphysema and high exercise capacity, mortality was higher in the surgery group than in the medical-therapy group (risk ratio, 2.06; P=0.02). LVRS, NETT Conclusions ◦ Overall, lung-volume–reduction surgery Increases the chance of improved exercise It does yield a survival advantage for patients with both predominantly upper-lobe emphysema and low base-line exercise capacity. Patients previously reported to be at high risk and those with non–upper-lobe emphysema and high base-line exercise capacity are poor candidates for lung-volume– reduction surgery, because of increased mortality and negligible functional gain. LVRS Patient Selection ◦ A systematic review proposed the following features, as determined by expert opinion, to be associated with better outcomes: Smoking-related emphysema Heterogeneous emphysema with surgically accessible "target" areas Bilateral surgery Good general fitness/condition and thoracic hyperinflation LVRS Patient Selection Endo-bronchial Valves Endo-bronchial valves (EBV) are one-way valves that prevent air from entering the airway distally but allow for ventilation of the expired gas and drainage of distal secretions. Two-valve designs have been studied in separate multicenter reports (Zephyr EBV, Pulmonx Corp and IBV, Spiration, Inc.). The Zephyr EBV The Zephyr EBV, formerly known as Emphasys EBV, consists of a stent-like self-expanding retainer made of nitinol, which is wrapped in molded silicone. In the center of the retainer is a duckbill one-way valve that allows outflow of gas and secretions during exhalation but does not permit air entry during inhalation. The EBV is compressed via a loader system, placed onto a delivery catheter, and a guide-wire directs this catheter to the targeted area, all via the working channel of a bronchoscope. The Zephyr EBV N Engl J Med 2010; 363:1233-1244September 23, 2010DOI: 10.1056/NEJMoa090092 Zephyr EBV, VENT The EBV valve was tested in The Endo-bronchial Valve for Emphysema Palliation Trial (VENT). A multicenter, randomized controlled trial of 321 subjects with severe heterogeneous emphysema (220 treated with Zephyr EBV and 101 treated as controls). At 6-month follow-up, the treatment group had statistically significant improvements in the primary endpoints of FEV1 (+6.8%,P=.002 ) and 6MWT (+5.8%,P=.019 ). Zephyr EBV, VENT There were also significant improvements in secondary outcomes of St. George’s Respiratory Questionnaire (SGRQ) and BODE index compared with control. The 6-month mortality was 2.8% among the treatment group (zero in the control group), and cumulative mortality rate over 1-year follow-up was 3.7% for the Zephyr group and 3.5% for the control group (P=1.000). Zephyr EBV, VENT Complications related to the device were ◦ Valve migration ◦ Pneumonia distal to the valve ◦ Granulation tissue In final review of various outcomes from this trial ◦ The FDA advisory panel recommended against approval of this device, citing that the benefits were not large enough to overcome the risks. IBV, Spiration The Intrabronchial Valve (IBV; Spiration) is also made of nitinol and has 5 distal anchors and 6 proximal support struts that are covered by a synthetic polyurethane polymer These struts expand to form an umbrella shape to allow for sealed placement in the airway. Air and mucus are able to flow around the edges of the membrane. The valve has two delivery system options via a loading device through the working channel of a flexible bronchoscope. Spiration IBV The largest trial reported An open-label study. A total of 98 patients were enrolled at 13 international centers over a 3-year period with the intent of bilateral treatment of upper lobe predominant emphysema. Bilateral treatment was done in 95 of the 98 patients, and a total of 659 valves were placed. While they did not find statistically significant improvements in spirometry and lung volume measurements at 3 and 6 month follow-up, the patients SGRQ decreased by greater than 4 (a 56% improvement) at 6 months. Spiration IBV There were a total of 8 pneumothoraces, one of which was a tension pneumothorax that occurred on post-procedure day 4 and resulted in the death of the patient. There were no episodes of valve migration or expectoration. The most common post-procedure adverse event was bronchospasm, which resolved after one bronchodilator treatment in 3 cases but required several repeated treatments in 2 other patients. In the latter two cases, the bronchospasm lasted for 24 to 48 hours, resolved after valve removal, and was assumed to be related to the valves. Current status of bronchoscopic lung volume reduction with endo-bronchial valve Methods ◦ Searches for appropriate studies were undertaken on PubMed and Clinical Trials Databases using the search terms COPD, emphysema, lung volume reduction and endobronchial valves Thorax. 2014 Mar;69(3):280-6. doi: 10.1136/thoraxjnl-2013-203743. Epub 2013 Sep 5. Current status of bronchoscopic lung volume reduction with endobronchial valves. Shah PL1, Herth FJ. Current status of bronchoscopic lung volume reduction with endo-bronchial valve Results ◦ The evidence from the randomized clinical trials suggests that complete lobar occlusion in the absence of collateral ventilation or where there is an intact lobar fissure are the key predictors for clinical success. ◦ Other indicators are greater heterogeneity in disease distribution between upper and lower lobes ◦ The proportion of patients that respond to treatment improves from 20% in the unselected population to 75% with appropriate patient selection ◦ The safety profile for endobronchial valves in this severely affected group of patients with emphysema was acceptable and the main adverse events observed were an excess of pneumothoraces. Thorax. 2014 Mar;69(3):280-6. doi: 10.1136/thoraxjnl-2013-203743. Epub 2013 Sep 5. Current status of bronchoscopic lung volume reduction with endobronchial valves. Shah PL1, Herth FJ. Current status of bronchoscopic lung volume reduction with endo-bronchial valve Conclusion ◦ Selected patients have the potential of significant benefit in terms of lung function, exercise capacity and possibly even survival ◦ These considerations are essential in-order to maximize patient benefit in a resource-limited environment and also to ensure that beneficial treatments are available for the appropriate patient Thorax. 2014 Mar;69(3):280-6. doi: 10.1136/thoraxjnl-2013-203743. Epub 2013 Sep 5. Current status of bronchoscopic lung volume reduction with endobronchial valves. Shah PL1, Herth FJ. This article describes first experiences in a patient with five endobronchial valves in the right upper lobe who needed urgent surgery due to lumbar disc herniation with neurological impairment. The use of broncho-dilating volatile anesthetics and adjusting the ventilatory settings with long expiration times and low peak pressure in a pressure controlled mode seems favorable in these patients. In conclusion the care of patients with implanted endobronchial valves after ELVR does not differ from COPD patients without ELVR. COPD Assessment of General operative risk Methodologies of Assessment ◦ Essential components of the preoperative assessment are a careful history physical examination assessment of the functional capacity Close attention should be paid to a history of smoking, dyspnea, cough and sputum production. Functional capacity can be assessed by the ASA questionnaire COPD Assessment of General Operative Risk The perioperative risk of venous thromboembolism and potential prophylactic strategies should be assessed for all patients. In patients with a known diagnosis of COPD, or those at increased risk for COPD, preoperative spirometry should be performed. ◦ Identification of severe airflow obstruction may be particularly important in patients who are candidates for upper abdominal or thoracic surgical procedures Analysis of arterial blood gas (ABG) composition should be available for patients with moderate-to-severe COPD. Since patients with COPD are at increased risk of pulmonary neoplasm and other pathologies, a preoperative chest radiography, if not recently performed, is reasonable Surgery in the COPD Patient Ophthalmologic procedures ◦ ◦ low mortality rate (<1%) cough may be of concern because of increased ocular pressure. ◦ Procedures involving the airway carry an increased risk of postoperative pneumonia Management of secretions in the patient who has undergone laryngectomy may require early postoperative humidification. Orthopaedic procedures ◦ ◦ Topical, ophthalmologic, β-blocker medications, used to reduce intraocular pressure, may precipitate bronchospasm and cardiorespiratory failure Head/neck procedures ◦ ◦ excessive suppression of cough may lead to retained secretions, atelectasis, pneumonitis and problems in gas exchange. Orthopedic procedures are associated with a relatively high frequency of venous thromboembolism In the patient with COPD, pulmonary embolism is associated with greater mortality Lower abdominal/pelvic surgery ◦ In general, COPD does not increase the risk of perioperative risk with lower abdominal procedures. Surgery in COPD Patient Upper abdominal surgery ◦ Patients who undergo surgery in the upper abdomen are at risk for perioperative pulmonary complications ◦ COPD independently increases this risk ◦ Complications are particularly liable to occur in persons with predisposing factors such as morbid obesity, cigarette smoking, heart disease and advanced age Cardiovascular surgery ◦ COPD is a common cause of perioperative pulmonary dysfunction in patients undergoing cardiac surgery ◦ Screening for COPD in this patient population is particularly important because COPD has been associated with prolonged intubation after cardiac surgery Abdominal vascular surgery ◦ Patients who undergo elective major abdominal vascular surgery are at high risk of postoperative pulmonary complications ◦ Patients with COPD are at particularly high risk ◦ Factors associated with the need for prolonged mechanical ventilation include a history of heavy cigarette smoking, preoperative arterial hypoxaemia and major intraoperative blood loss Surgery in COPD patient Lung surgery ◦ Preoperative pulmonary function studies have a welldocumented role in the evaluation of patients who are to undergo lung surgery Procedure-related issues ◦ Thoracotomy has a reversible (several months) adverse effect on lung function ◦ Lung resection Lobectomy results in an additional ?10% reduction in forced vital capacity (FVC) at 6 months after surgery Pneumonectomy usually causes a permanent reduction of about 30% in all lung function. This decrement in lung function can prove devastating to COPD patients COPD and Lung Resection Patients with preserved lung function should tolerate resection well in the absence of other comorbid conditions. Preoperative values of forced expiratory volume in one second (FEV1) >2 L (or >80 percent predicted) and DLCO >80 percent predicted suggest that the patient should be able to tolerate surgery including pneumonectomy. For patients with preoperative FEV1 <2 L (or <80 percent predicted) or DLCO <80 percent predicted, the predicted postoperative (PPO) FEV1 and DLCO should be calculated, based upon the preoperative values and the fractional functional contribution of the lung to be resected. ◦ PPO FEV1 = preoperative FEV1 x (1 – y/z) where y = number of functional or unobstructed lung segments to be removed, and z = total number of functional segments (typically 19) COPD and Lung Resection Cardiopulmonary exercise testing (CPET) is useful when the results of PPO FEV1, PPO DLCO, and/or low technology exercise testing do not clearly define the patient’s risk as either high or low. Patients who can achieve a VO2 max >20 mL/kg per minute are likely to have an acceptable rate of postoperative complications, whereas those with a value <10 mL/kg per min (or less than 35 percent predicted) are probably best managed by nonsurgical modalities. For those with VO2 max values in between 10 and 20 mL/kg per minute, the predicted postoperative (PPO) VO2 max is calculated. If the PPO VO2 max is <10 mL/kg per min or <35 percent, surgical candidacy is poor and nonresectional options should be sought. On the other hand, if the PPO VO2 max is ≥10 mL/kg per min or ≥35 percent, resection is not absolutely contraindicated, but the patient must understand the higher risk if either the PPO FEV1 or DLCO is <30 percent predicted. Peri-operative Management General factors include the following. ◦ Every effort should be made to aid with smoking cessation Smoking cessation at least 4-8 weeks preoperatively is optimal. ◦ Optimization of lung function using inhaled bronchodilators (in patients with severe COPD can decrease postoperative complications. ◦ Oral Corticosteroids. Pulmonary rehabilitation should be considered in high-risk patients undergoing elective procedures. ◦ Pre- and postoperative pulmonary rehabilitation have been shown to decrease postoperative pulmonary complications after abdominal surgery Intra-operative Management The COPD patient may be more sensitive to the ventilatory depressant effects of the analgesic, regional and general anaesthetic agents used . Volatile anesthetics, intravenous anaesthetics and neuromuscular blocking agents vary in their ability to provoke unwanted autonomic effects and alter airway reactivity . The risk of pulmonary complications may be higher with the use of the long-acting neuromuscular blocker pancuronium than shorteracting atracurium or vecuronium Intraoperative Management The role of general versus regional anaesthesia remains controversial. A meta-analysis suggested that neuroaxial blockade with epidural or spinal anaesthesia decrease postoperative mortality, deep venous thrombosis, pulmonary embolism, transfusion requirements, pneumonia and respiratory depression A subsequent randomized trial of intraoperative and postoperative epidural analgesia plus general anaesthesia for upper abdominal surgery in high-risk patients (7-8% with severe COPD) noted only a reduction in postoperative respiratory failure (number needed to treat to prevent one episode of respiratory failure was 15). Intraoperative Management In COPD patients, the combination of thoracic epidural and general anesthesia may result in less shunting and better oxygenation during thoracic surgical procedures. Thoracic epidural anaesthesia appears to have only limited deleterious effects on pulmonary function in patients with severe COPD and has been used as the primary mode of anaesthesia for COPD patients undergoing chest wall surgery . The immediate postoperative recovery period is a period of high risk because of the possibilities of respiratory muscle dysfunction, acidemia, hypoxaemia and hypoventilation. Postoperative Management Early mobilization, deep breathing, intermittent positive-pressure breathing or incentive spirometry have been reported to decrease postoperative complications after upper abdominal surgery. A necessary component of postoperative management is effective analgesia. ◦ Epidural administration may offer superior analgesia with less sedation by promoting patient mobility and deep breathing . Indications for postoperative mechanical ventilation are respiratory failure with retained secretions, atelectasis and pneumonia. Continuation of preoperatively prescribed respiratory medications is standard therapy. 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The exact prevalence of pulmonary hypertension resulting from COPD remains unknown. A few studies based on hospitalized patients have estimated the prevalence of PH secondary to COPD as defined by a mean PAP >20 mmHg to range between 35% and 90%. COPD and Pulmonary Hypertension The mechanisms of development of PH in COPD patients include ◦ increase in pulmonary vascular resistance secondary to alveolar hypoxia ◦ increase in pulmonary capillary wedge pressure during exercise in patients with severe emphysema and hyperinflation. PH in COPD patients can be divided into two main features, ◦ The first one occurring at rest in the setting of stable COPD. The majority of these patients will have a mild degree of PH with an average mean PAP of 25 to 30 mmHg. However if the mean PAP is >40 mmHg, it is usually associated with cardiopulmonary disease, acute exacerbation, or disproportionate PH which will be discussed separately. ◦ The second feature includes worsening of PH during exercise, sleep or COPD exacerbation. COPD and Pulmonary Hypertension Worsening of PH with a marked increase in mean PAP is noted in patients with advanced COPD and PH at rest. In these patients, a mean PAP of 25 mmHg during rest may increase to 50 to 60 mmHg during 30 to 40 watt exercise, sleep or acute COPD exacerbations, which lead to symptoms of dyspnea on even daily activities like climbing or walking COPD and Pulmonary Hypertension Right heart catheterization (RHC) remains the gold standard for diagnosis of PH in these patients RHC can be performed at rest, during steady-state exercise, and after therapeutic interventions (vasodilators) There are no clear guidelines regarding indications of treatment of PH in COPD patients The necessity of treatment of mild or moderate PH in these patients remain questionable, however some may argue that acute increase in PAP with worsening of PH during acute COPD exacerbations and/or exercise may contribute to development of right-sided heart failure. COPD and Pulmonary Hypertension Prior to initiation of treatment, all patients must have RHC to evaluate PH severity and to rule out other explanations for dyspnea such as left sided heart failure. Treatment may include oxygen therapy and pulmonary vasodilators. Long-term oxygen therapy should be prescribed as clinically indicated since it has been shown to reverse and /or stabilize PH over a period of 2 to 6 years. COPD and Pulmonary Hypertension PAH specific medical therapy including prostacyclin analogues, phosphodiesterase-5 inhibitors and endothelin receptor antagonists were tested in randomized controlled trials, leading to approval of several drugs. However a recent study included COPD patients with mild resting PH or no PH treated with Bosentan or placebo showed no improvement in pulmonary hemodynamics but a worsening of gas exchange abnormalities. Thank You