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CLINICAL PRACTICE GUIDELINESIN THE DIAGNOSIS AND MANAGEMENT OF

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)IN THE PHILIPPINES

Report of the Council on COPD & Pulmonary RehabilitationPhilippine College of Chest Physicians

Second Update: 2005 Version

PROPONENTS:

Chair:Norberto A. Francisco, MD, FPCCP

Members:Deogracias Abe II, MDEthel Añonuevo, MDJoven S. Araneta, MDTito A. Atienza, MD, FPCCPMa. Rowena G. Balcita, MDDaphne D. Bate, MD, FPCCPAgnes Lucy G. Belleza, MD, FPCCPVeyda Christine Bringas, MDCeleste Mae Campomanes, MD, FPCCPNolasco Capati Jr., MDMa. Teresa V. Catacutan, MDChona De Vera, MDVirginia Delos Reyes, MD, FPCCPOscar Ferdinand L. Feliciano, MDLenora C. Fernandez, MD, FPCCPClaudette Gabrillo, MDElmer Garcia, MD, FPCCPSuset Gargalicana, MDAileen Guzman-Banzon, MD, FPCCPRenato Herradura, MD, FPCCPCharina N. Hipolito, MDLuisito F. Idolor, MD, FPCCPManuel Antonio Ko, MDRomeo Labao Jr., MDJosefina Lagunzad, MDIsaias A. Lanzona, MD, FPCCP

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Caesar Julius Ligo, MD, FPCCPLai Lee L. Lim, MDPerla Manlapaz, MD, FPCCPJohn Clifton Martyr, MDBuenaventura Medina, MD, FPCCPCaesar Mendoza, MD, FPCCPJenny Mendoza, MD, FPCCPJennifer Ann Mendoza-Wi, MD, FPCCPJessie F. Orcasitas, MDRodolfo Pagcatipunan Jr., MDRolando Perez, MD, FPCCPMary Alexis Pollentes, MD, FPCCPPercival Punzal, MD, FPCCPEvelyn Ragos, MDTomas M. Realiza, MD, FPCCPRhoderick Ian Reyes, MD, FPCCPJoel M. Santiaguel, MD, FPCCPMa. Bella R. Siasoco, MD, FPCCPBobbin Sy, MD, FPCCPSullian Sy-Naval, MD, FPCCPJose Edzel V. Tamayo, MD, FPCCPMarietta Tan-Tanchoco, MD, FPCCPDennis Teo, MD, FPCCPRomulo Uy, MD, FPCCP

Editor:Lenora C. Fernandez, MD, FPCCP

First Update: 2003 Version

PROPONENTS:

Chair:Lenora C. Fernandez, MD, FPCCPInterim Chair:Tito C. Atienza, MD, FPCCPCo-Chair:Norberto A. Francisco, MD, FPCCP

Members:Jubert Benedicto MD.Celeste Mae Campomanes MD, FPCCPAnnette David-Rubio MDVirginia delos Reyes MD

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Elmer Garcia MD, FPCCPRenato Herradura MD, FPCCPLuisito Idolor MD, FPCCPIsaias Lanzona MD, FPCCPJulius Ligo MD, FPCCPPerla Manlapaz MD, FPCCPBuenaventura Medina Jr., MDCesar Mendoza MD, FPCCPJenny Mendoza MDJennifer Ann Mendoza-Wi, MD, FPCCPRodolfo Pagcatipunan MDRolando Perez, MD, FPCCPPercival Punzal MD, FPCCPTomas Realiza MD, FPCCPRhoderick Ian Reyes MDJoel Santiaguel MDMa. Bella Siasoco MD, FPCCPBobbin Sy, MD, FPCCPSullian Sy-Naval MD, FPCCPMarietta Tanchoco-Tan MD, FPCCPDennis Teo MD, FPCCPRomulo Uy MD, FPCCP

Advisers:Rodolfo Carungin, MD, FPCCPTeresita de Guia MD, FPCCPCamilo Roa, Jr. MD, FPCCPDaniel Tan MD, FPCCPCharles Yu MD, FPCCP

Family Medicine Practitioner Advisers:Erle Castillo MD, FPAFPLeilani Nicodemus MD, FPAFP

1999 (First) Version

Proponents:

Chair:Percival A. Punzal, MD

Members:Norberto A. Francisco, MD.Aileen V. Guzman, MD.

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Abner T. Koh, MD.Isaias A. Lanzona, MD.Buenaventura Medina Jr., MD.Ma. Bella R. Siasoco, MD.

Advisers:Teresita de Guia, MD.Rodolfo Carungin, MD.Camilo Roa Jr., MD.Daniel Tan, MD.Renato Dantes, MD.

Member Societies/Groups/Individuals of Multisectoral Consultative Groups:Philippine College of Chest PhysiciansPhilippine Academy of Family PhysiciansPhilippine Society of Rehabilitation MedicinePhilippine Association of Pulmonary CarePhilippine Association of Thoracic and Cardiovascular Surgery, Inc.Department of HealthPhilippine Nurses AssociationNutritionistsPriest

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TABLE OF CONTENTS: PAGEI. IntroductionII. What is COPD?III. What are the risk factors for COPD?IV. How do we diagnose COPD?

A. Detection of COPDB. Confirmation of COPDC. Additional investigationsD. Grading of COPD severityE. How is COPD differentiated from

other common causes ofobstructive lung diseases in thePhilippines, specifically asthma &bronchiectasis?

F. Ongoing monitoring and assessmentV. How do we manage patients with

stable COPD?A. Smoking cessationB. Pharmacologic management

1. General principles ofpharmacologic management

2. Pharmacologic agentsC. Non-pharmacologic managementD. Management continuum for

Stable COPDVI. How de we management a COPD patient in

Acute exacerbation?A. Definition of COPD in acute exacerbationB. Common causes of acute exacerbation

of COPDC. Severity classification of COPD in acute

exacerbationD. Home management

1. Bronchodilator therapy2. Antibiotics3. Glucocorticosteroids

E. Hospital management1. Initial management of exacerbations

of COPD in the emergencydepartment or the hospital

3. The inclusion criteria for admission in theIntensive Care Unit (ICU)

4. Indications for hospital assessment oradmission

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F. Intensive care unit management1. Candidates for NIPPV2. Indications for starting invasive

mechanical ventilationG. Hospital discharge and follow-up

1. Discharge criteria2. Follow-up assessment

H. Indications for Specialist ReferralI. Ethical issues

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I. INTRODUCTION

Chronic Obstructive Pulmonary Disease (COPD) is one of the mostimportant diseases of the 21st century, being a major cause of death anddisability. Most epidemiological studies have found that the prevalence ofmorbidity and mortality due to COPD have increased over time and are greaterin men than in women. The impact of COPD is not only confined to its ill effectson the individual’s health but also permeates into the social and economicaspects as well.

The 1998 World Health Organization Report states that non-communicablediseases, including COPD, is the cause of nearly 40% of all deaths in developingcountries and that these areas account for 67% of all COPD deaths worldwide.1

In these developing countries, the indirect cost of COPD from loss of work andproductivity may be more important than the cost of medical care. A localstudy2 done in a rural community in Laguna, Philippines estimated theprevalence of COPD based on spirometric measurements to be 3.7%. In arecent workshop in the Asia Pacific region3, the prevalence of COPD in thePhilippines was cited at 6.3% utilizing data from a study of Dans and colleagues.4

In response to the need to help prevent and manage COPD better, thePhilippine College of Chest Physicians published the Philippine Consensus Reporton COPD in 1999 (see Appendix 1). However, with the publication of the GlobalInitiative for Chronic Obstructive Lung Disease (GOLD) Workshop Report entitled“Global Strategy for the Diagnosis, Management, and Prevention of COPD”, theproponents of the Philippine Consensus Report on COPD updated theirguidelines to cater to the specific needs of the Philippines as a developingcountry. The proponents realize that not all of the recommendations from theGOLD document can be adopted considering limitations in terms of thePhilippines’ local resources. This lack of certain resources, such as the availabilityof spirometry only in the major cities, was taken into consideration. This guidelineis intended for the use of practicing physicians and other health professionalsinvolved in the care of patients with chronic obstructive pulmonary disease(COPD). The goals of this practice guideline are to:

1. assist primary health care practitioners in identifying and initiatingmanagement of patients with COPD.

2. assist hospital-based physicians in providing appropriate and cost-effective care for COPD patients.

3. recommend measures for the prevention of further deterioration of lungfunction and subsequent complications; and in the improvement in thequality of life of COPD patients.

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4. assist allied health care workers in the care of COPD patients.5. identify areas for further research in the diagnosis and management of

COPD in the Philippines.

The process used in updating this practice guideline was by: (a) selection ofa Core Group to review the previous guideline and identify topics/areas thatneeded revision, (b) selection of committee members to handle each identifiedtopic, (c) search for recent data in the literature, (d) grading of availableevidence, (e) assessment of locally available resources, (f) formulation,presentation and revision of draft recommendations, and (g) formulation of finalstatements.

Levels of evidence are assigned to the statements, where appropriate,following the system of the US National Heart, Lung, and Blood Institute (NHLBI)which is comparable to the classification used in the 1999 practice guideline:

DESCRIPTION OF LEVELS OF EVIDENCE

EvidenceCategory

Sources of Evidence Definition

A Randomized controlledtrials (RCTs). Rich bodyof data

Evidence is from endpoints of well-designed RCT’s that provide a consistentpattern of findings in the population forwhich the recommendation is made.Category A requires substantial numbers ofstudies involving substantial numbers ofparticipants.

B Randomized controlledtrials (RCTs). Limitedbody of data

Evidence is from endpoints of interventionstudies that include only a limited numberof patients, post-hoc or subgroup analysisof RCTs, or meta-analysis of RCT’s. Ingeneral, Category B pertains when fewrandomized trials exist, they are small insize, they were undertaken in a populationthat differs from the target population ofthe recommendation, or the results aresomewhat inconsistent.

C Nonrandomized trials.Observational studies

Evidence is from outcomes of uncontrolledor nonrandomized trials or fromobservational studies.

D Panel consensusjudgment.

This category is used only in cases wherethe provision of some guidance wasdeemed valuable but the clinical literatureaddressing the subject was deemedinsufficient to justify placement in one of

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the other categories. The Panel Consensusis based on clinical experience orknowledge that does not meet the above-listed criteria.

Discussion on the most appropriate recommendations with the advisersand stakeholders was lengthy and painstaking. The ultimate deciding factor inall the recommendations was what could benefit the typical Filipino COPDpatient most.

This document is divided into five parts that discusses the (1) definition ofCOPD, (2) risk factors for developing COPD, (3) diagnosis, classification andmonitoring of COPD, (4) management of stable COPD, (5) and management ofCOPD in acute exacerbation. Recommendations for the aspects of COPDneeding further research and references used are placed at the end of eachchapter.

The sections are written in a brief and concise manner to help the readerimbibe the key points quickly so that the document can be used at bedside orin the clinics. For further elaboration of the guidelines, the proponents will bedisseminating the document through focused group discussions on anationwide basis starting Year 2003.

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II. WHAT IS COPD?

Key Points:

COPD is a preventable and treatable disease characterized by airflowlimitation that is not fully reversible.

The airflow limitation is usually both progressive and associated with anabnormal inflammatory response of the lungs to noxious particles or gases.

Definition & Pathophysiology

COPD is a preventable and treatable disease state characterized byairflow limitation that is not fully reversible. The airflow limitation is usually bothprogressive and associated with an abnormal inflammatory response of thelungs to noxious particles or gases.

The constant pathologic abnormality in smokers is an inflammatoryreaction in the airways and parenchyma consisting of neutrophils and alveolarmacrophages. In addition to inflammation, oxidative stress and imbalance ofproteinases and antiproteinases in the lung are also implicated in thedevelopment of COPD.

The ensuing pathologic changes in COPD involve the central andperipheral airways, lung parenchyma and pulmonary vasculature. Mucus glandhypertrophy, goblet cell metaplasia and airway thickening occur in the centralairways and these are responsible for the chronic cough and sputum productionthat are characteristic of COPD. The major site of airways obstruction, however,occurs in the peripheral airways mainly due to airway wall thickening andfibrosis. Destruction of the lung parenchyma leads to the pathology ofemphysema or dilatation and destruction of respiratory bronchioles.Subsequent gas exchange abnormalities and eventual pulmonary hypertensionand right heart failure (cor pulmonale) result as the disease progresses.

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III. WHAT ARE THE RISK FACTORS FOR COPD?

Key Points

Cigarette smoke is the major risk factor for COPD

Since cigarette smoking is the most important risk factor for COPD,smoking prevention and cessation should be given the utmost priority.

Modifying factors other than smoking have been shown to have astrong association with the development of COPD

Disease prevention by avoidance of risk factors is of crucial importancebecause of the irreversible and progressive nature of COPD.

1. SMOKING

Tobacco use is the single most important factor in the pathogenesis ofCOPD and it causes 80% to 90% of COPD cases.5 As graphically represented inthe survival curve of Fletcher and Peto (Figure 3.1)6, only a portion of chronicsmokers show a rate of decline of lung function that is typical of patients whopresent with breathlessness due to COPD. Susceptible smokers have anaccelerated rate of decline of lung function (50-90 mL of Forced ExpiratoryVolume at 1 second (FEV1)/year compared with 20-30 mL of FEV1/year after theage of 30 years in non-smokers). Subjects with COPD who stop smoking have aslower rate of progression of their disease which may approach the expecteddecline in FEV1 in non-smokers. Despite the often cited and scientificallyassociated relation between smoking and airway obstruction, only 10-20% ofchronic heavy smokers ever develop symptomatic COPD.7 This indicates thatthere are genetic and/or environmental factors which contribute to thedevelopment of COPD.

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Figure 3.1. Graph of survival from Fletcher C, Peto R, Br Med J, 1:1645-1648, 1977

2. SECONDHAND SMOKE

There is a small but significant difference in the prevalence of respiratorysymptoms and lung function in adults and children who are regularly exposed tosecondhand smoke.8 It is still unclear whether secondhand smoke causes COPD.

3. ALPHA-1 ANTITRYPSIN DEFICIENCY

Another well established9 risk factor for the development of COPD is adeficiency in the function and/or quantity of the protective protease inhibitor,alpha-1 antitrypsin (AAT). This accounts for 5% or less of all cases of COPD andthese cases are mostly found in the Western hemisphere.10 This is an autosomalrecessive (PiZZ genotype) disorder.

4. AIR POLLUTION AND OCCUPATIONAL EXPOSURE

Whether atmospheric pollution itself can cause or contribute to thedevelopment of COPD or not is still uncertain.

Outdoor air pollution may vary in different areas. As with the problem ofsmoking, there will be individuals who will be more susceptible to the effects ofatmospheric pollution than others. An epidemiologic study in the Philippines11

comparing the effect of outdoor air pollution among jeepney drivers, air-conditioned bus drivers and commuters in Metro Manila showed thatcumulative exposure levels to air pollutants far exceeded standard levels and

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was significantly higher among jeepney drivers. The prevalence of COPDamong jeepney drivers was 32.5%, 16.4% for air-conditioned bus drivers and14.8% for commuters. Jeepney drivers had an odds ratio of 2.33 for developingCOPD as compared to air-conditioned bus drivers and commuters. Theprevalence of smoking, however, among jeepney drivers was 69.4% and thisprobably affected to a significant degree the increased probability of jeepneydrivers to develop COPD.

Occupational exposure. Any occupation wherein the immediate environmentis polluted increases the risk of developing COPD. In addition, there is evidencethat cadmium and silica also increases the risk of development of COPD.Occupations at risk include coal miners, construction workers who handlecement, metal workers, grain handlers, cotton workers and workers in papermills. However, the effect of smoking far outweighs any influences from the workenvironment.

Indoor air pollution. Numerous sources of airborne contaminants have beenidentified in indoor environments and include pollutants found in home, officeand transportation environments. In the home, the principal combustionsources are tobacco-smoking, gas cooking stoves, unvented kerosene heatersand biomass fuels (Table 3.1). Wood burning in stoves also affects indoor airquality.12

Table 3.1

Common Biomass Fuels1

Crop Residues – sugar cane bagasse Agricultural waste – coconut husk, rice straw, palay shell Firewood Charcoal

5. SOCIOECONOMIC STATUS

Studies attempting to identify a relationship between COPD andsocioeconomic status often encounter an association between social class andindoor air pollution, with COPD being more prevalent in the lowersocioeconomic strata.13 This may be related to poor housing condition,nutritional status and use of fossil fuels without adequate ventilation. Also, there isa higher prevalence of smoking in the lower socioeconomic strata, and they are

1 Adapted from Biofuels, ,Air Pollution and Health Smith, East-West Centre, Honolulu, 1987

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more likely to be employed in jobs where they may be at risk from occupationalexposure.

6. INFECTIONS

The role of viral upper and lower respiratory tract infections in thepathogenesis of COPD remains to be clarified. Viral infections in the lungenhance inflammation and predispose to bronchial hyperreactivity.Epidemiologic studies suggest that childhood infections, usually due toadenovirus and respiratory syncitial virus, are independent risk factors for thedevelopment of COPD in adulthood.14,15 Furthermore, adenoviral DNA isfrequently found in the lungs of heavy smokers.14 Once COPD is established,repeated infectious exacerbations may accelerate the decline in lung function.

PREVENTION OF RISK FACTORS

Disease prevention by avoidance of risk factors is of primary importancebecause of the irreversible and progressive nature of COPD. Since cigarettesmoking is the most important risk factor for COPD, smoking prevention andcessation should be given the utmost priority in decreasing the incidence of thedisease. Reduction in total personal exposure to dusts, fumes, and gases in theoutdoor, indoor, and occupational setting should also be addressed whenconsidered to be significant. Currently, there is inadequate basis forrecommending respiratory protective equipment or air cleaners for use in theworkplace or home as means to minimize contact with noxious particles andgases. Avoidance of exposure to these substances is strongly advised.

RESEARCH RECOMMENDATIONS

1. Philippine prevalence studies on COPD

Available local studies on nationwide prevalence are lacking; thoseavailable are only estimated or extrapolated values based on theprevalence of smoking

2. Longitudinal studies demonstrating the course of COPD in a variety ofpopulations exposed to various risk factors

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No local studies have been undertaken to quantify the relationshipbetween COPD and risk factors other than smoking e.g. biomass fuels,occupational pollutants, socioeconomic status.

3. Burden of Illness Study

Cost of care for COPD is perceived to be high but there are no localstudies documenting the overall impact of this disease on the individualand national level.

4. Studies on the role of secondhand smoke as a cause of COPD

5. Determine the incidence of AAT Deficiency among Filipinoemphysematous patients

AAT was previously thought to be a condition of Caucasions; however, aJapanese study has suggested that a form of this condition may exist as amutation in Asians.

REFERENCES:

1. The World Health Report 1998- Life in the 21st century- a vision for all by the World HealthOrganization.

2. Yu CY, Chavez JC, Blanco JB et al. Prevalence of chronic obstructive pulmonary disease in arural Philippine community barangay Banca-Banca, Victoria, Laguna. Phil J of Chest Diseases1987; 137-151.

3. Seale JP. The prevalence of COPD in Asia Pacific. RespirAsia Report Issue 1 January 2002.

4. Dans A, Fernandez L, Fajutrao et al. The economic impact of smoking in the Philippines. Phil Jof Int Med Nov-Dec 1999; 37(6):261-68.

5. US Surgeon General. The health consequences of smoking: chronic obstructive lung disease.US Department of Health and Human Research, 84-50205, 1984.

6. Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ 1977; 1:1645-8.

7. Roth MD, Tashkin DP, Arora A, et al. Airway inflammation in the young and tobacco smokers.Am J Respir Crit Care Med 1998; 157: 928-37.

8. Leuenberger P, Schwartz J, Ackermann-Liebrich U, et al. Passive smoking exposure in adultsand chronic respiratory symptoms (SAPALDIA study). Am J Respir Crit Care Med 1994; 150: 1222-8.

9. Silvermann EK, Chapman HA, Drazen JM, et al. Genetic epidemiology of severe, early-onsetchronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157: 1770-1778.

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10. Sandford AJ, Weir TD, Pare PD. Genetic risk factors for chronic obstructive pulmonary disease.Eur Respir J 1997; 10: 1380-1391.

11. Subida, Torres, Borja, Tanchuco. Epidemiology of chronic respiratory symptoms & illnessamong jeepney drivers, airconditioned bus drivers and commuters exposed to vehicularemissions in Metro Manila, 1990-91. unpublished.

12. Dennis RJ, Maldonado D, Norman S et al. Woodsmoke exposure and risk for obstructiveairways disease among women. Chest 1996; 109: 115-119.

13. Prescott E, Lange P, Vestbo J. Socioeconomic status, lung function, and admission to hospitalfor COPD: results from the Copenhagen City Heart study. Eur Respir J 1999; 13: 1109-1114.

14. Tager IB, Speizer FE, et al. The relationship between respiratory illness in childhood andchronic airflow obstruction in adults. Am Rev Resp Dis 1983; 127: 508-523.

15. Gold DR, Tager IB, Weiss ST. Acute lower respiratory illness in childhood as predictor of lungobstruction. Am Rev Resp Dis 1984; 129: 412-422.

16. Samet JM, Marbury MC, Spengler JD. Health effects and sources of indoor air pollution. AmRev Resp Dis 1987; 136: 1486-1503.

17. Matsuse T, Hayashi S, Kuwano K, et al. Latent adenoviral infection in the pathogenesis ofchronic airways obstruction. Am Rev Resp Dis 1992; 146: 177-184.

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IV. HOW DO WE DIAGNOSE COPD?

KEY POINTS:

A diagnosis of COPD is considered in any patient who:

Is 40 years or older Has cough, sputum production or dyspnea Has a history of exposure to risk factors for the disease

The diagnosis is confirmed by a postbronchodilator FEV1/FVC <70%.

Once COPD is diagnosed, the severity of the disease can be classifiedinto mild (Stage I), moderate (Stage II), severe (Stage III) and verysevere (Stage IV) based on the patient’s postbronchodilator FEV1value, signs and symptoms.

Once COPD is detected and confirmed, ongoing monitoring andassessment should include evaluation of: (1) continued exposure to riskfactors, especially tobacco smoke; (2) disease progression anddevelopment of complications; (3) pharmacotherapy and othermedical treatment; (4) exacerbation history; (5) comorbidities.

A. DETECTION OF COPD

AgeThe disease commonly appears in the fifth decade of life. It is rare to

encounter COPD in patients younger than 40 years old1.

SymptomsCOPD patients usually develop cough as the initial symptom2. Acute

chest illnesses characterized by increased cough, purulent sputum, wheezing,dyspnea, and occasionally fever may occur intermittently. Progressive dyspneaworsening over a period of months or years, is a typical feature of COPD.5 Inthe advanced stage of the disease, cor pulmonale with right heart failure andedema may develop. Cyanosis may also be present especially during acuteexacerbations.

Risk factorsCigarette smoking is the single most important factor in the pathogenesis

of COPD, and accounts for 80-90% of the risk of developing COPD. In addition,

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attention has focused on bronchial hyperreactivity, secondhand smoke, airpollution, and alpha-1-antitrypsin deficiency. Although alpha-1-antitrypsindeficiency is of comparable importance with tobacco smoking, this onlyaccounts for < 1 % of COPD. Little data is available to identify personssusceptible to develop COPD when exposed to these risk factors.

Physical ExaminationThe physical examination is not a sensitive means of detecting airflow

obstruction8. Among the physical findings, wheezing during quiet breathing11

and prolonged expiratory time (> 5 seconds) are useful indicators of airflowlimitation. These signs, however, are of no value as guides to severity and theirabsence does not exclude COPD.9

B. CONFIRMATION OF COPD

SPIROMETRY

For any individual suspected of COPD, a postbronchodilator FEV1/Forced VitalCapacity (FVC) <70% confirms the diagnosis.

The following diagram is suggested in order to arrive at a diagnosis of COPD:

SymptomsCoughDyspneaSputum production

Exposure torisk factors

COPD Suspect

Spirometry

Post-bronchodilatorFEV1/FVC < 70%

Post-BronchodilatorFEV1/FVC > 70%

COPD Not COPD

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Figure 4.1. Diagram for the Diagnosis of COPD.

Spirometry should measure the maximal volume of air forcibly exhaled from thepoint of maximal inspiration (forced vital capacity, FVC), the volume of airexhaled during the first second of this maneuver (forced expiratory volume inone second, FEV1), and the ratio of these two measurements (FEV1/FVC) shouldbe calculated 19. Patients with COPD typically show a decrease in both FEV1

and FVC. The degree of abnormality in the FEV1 generally reflects the severity ofCOPD.

Assessment of airflow obstruction before and after giving a short-actingbronchodilator (Bronchodilator Reversibility Testing), at the time of diagnosis, isrecommended. This is to obtain the post-bronchodilator FEV1 and FVC valuesthat will confirm the diagnosis of COPD20. The presence of a postbronchodilatorFEV1/FVC<70% confirms the presence of COPD where airflow limitation is not fullyreversible11.

The Bronchodilator Reversibility Testing is also helpful in distinguishing theasthmatic from the COPD patient 11,21,22. If FEV1 returns to the predicted normalrange after administration of a bronchodilator, the patient’s airflow limitation ismost likely due to asthma.

A protocol for the performance of Bronchodilator Reversibility Testing is listed inFig. 4.2 11.

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Figure 4.2. Bronchodilator Reversibility Testing

Preparation1. The test should be performed when patients are clinically stable and free from infection.

2. Patients should not have taken inhaled short-acting bronchodilators in the previous six hours,long-acting Beta-2 (B2) agonists in the previous twelve hours, or sustained release theophyllines in theprevious 24 hours.

Spirometry1. FEV1 & FVC should be measured before a bronchodilator is given.

2. The bronchodilator should be given by metered dose inhaler or by nebulizer.

3. Suitable dosage protocols for bronchodilators are 400 micrograms of B2-agonists, 80 microgramsof anticholinergic agents, or the two combined. FEV1 & FVC should be measured again 30-45 minutes after thebronchodilator is given.

Results1. A postbronchodilator FEV1/FVC < 70% confirms the diagnosis of COPD.

2. An increase in the FEV1 that is both greater than 200 ml and 12% above pre-bronchodilator FEV1 isconsidered a significant bronchodilator response.

C. ADDITIONAL INVESTIGATIONS

Chest radiograph

The standard postero-anterior and lateral chest radiograph is useful in the initialassessment of COPD patients to exclude or identify other conditions such astuberculosis, lung cancer, pneumothorax, or pneumonia. Chest X-ray findingsthat may be suggestive of COPD include hyperlucency of the lungs, rapidtapering of the vascular markings, and signs of hyperinflation (flattenedhemidiaphragms, and an increase in the volume of the retrosternal space)11. Anormal Chest X-ray, however, does not rule out the diagnosis of COPD.

Arterial blood gas measurement

Measurement of arterial blood gases with the patient breathing room air isrecommended in the assessment of patients with moderate to severe COPD18

when signs of right heart failure or respiratory distress are present. As the diseaseprogresses, hypoxemia becomes more severe and hypercapnia supervenes.

Peak flow determination

The definite correlation between peak expiratory flow rate (PEF) and FEV1 hasnot yet been proven since PEF may underestimate the degree of airflow

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obstruction6. Therefore, the use of peak expiratory flow rate determination inconfirming the diagnosis of COPD is not recommended.

Computed Tomography

Computed tomography (CT) scanning is not recommended in the routineassessment of COPD. Its role is limited to the preoperative evaluation of patientswith COPD who are about to undergo surgical procedures such as bullectomyor lung volume reduction surgery11,23.

Alpha-1 antitrypsin deficiency screening

Alpha-1-antitrypsin deficiency screening may be valuable to identify coexistingalpha-1 antitrypsin deficiency in patients who develop COPD at a young age(<45 years) or among those who have a strong family history of the disease11.However, this test is not available in the local setting.

D. GRADING OF COPD SEVERITY

Several practice guidelines have different ways of grading the severity of COPDand apparently depends on the different needs of each country. The mostrecent classification proposed by the GOLD Workshop Report “is a pragmaticapproach aimed at practical implementation and should only be regarded asan educational tool, and a very general indication of the approach tomanagement.” 11

The spirometric classification in the GOLD document has been shown to predicthealth status, utilization of healthcare resources, exacerbation occurrence, andmortality among COPD patients 27-29. It is, therefore, also adopted in thisdocument to facilitate the grading of severity of a patient’s COPD. In thePhilippines, however, it is an accepted reality that a significant number of healthworkers providing care to COPD patients may have limited access tospirometers. In such a situation, clinical features can aid in determining theseverity of COPD. In this guideline, the clinical signs and symptoms from theBritish Thoracic Society guidelines24 were utilized in the severity classificationbased on the previous clinical experience with Filipino COPD patients 25.

The body mass index and dyspnea have also proved useful in predictingoutcomes such as survival in COPD and would warrant further validation amongFilipino patients26.

It cannot be overemphasized that the identification of individuals in Stage 0 orthose who have or have been exposed to the risk factors for COPD, may or may

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not have the signs and symptoms of COPD and still have no obstructive defecton spirometry is considered to be very important. This is one of the most crucialperiod when interventions to reduce or remove these risk factors (e.g. smokingcessation, change in occupation, etc.) will have the greatest impact inpreventing the occurrence of COPD.

The proposed classification of COPD is shown in Table 4.1 below.

Table 4.1. Grading of COPD SeverityStage Spirometry* Signs/Symptoms0: At Risk Normal spirometry

FEV1/FVC > 70% No abnormal signs Smoker’s cough or Chronic sputum

productionI: Mild COPD FEV1/FVC < 70%

FEV1 > 80%predicted

No abnormal signs With or without symptoms

of:- smoker’s cough- Little or no

breathlessnessII: Moderate

COPD FEV1/FVC <70%; FEV1>50% but

< 80% predicted

Variable abnormal signs(general reduction inbreath sounds, presence ofwheezes)

With or without symptomsof:

- smoker’s cough- Little or no

breathlessnessIII: SevereCOPD

FEV1/FVC <70% FEV1>30% but

<50% predicted

Variable abnormal signs(general reduction inbreath sounds, presence ofwheezes)

Breathlessness on exertion Cough and chronic

sputum production

IV: VerySevereCOPD

FEV1/FVC < 70% FEV1 < 30%

predicted or FEV1 < 50%

predicted withrespiratory failure orclinical signs of rightheart failure

Breathlessness on anyexertion/at rest

Wheeze and cough oftenprominent

Lung overinflation usual;cyanosis; peripheraledema and polycythemiain advanced disease,especially duringexacerbation

*All FEV1 values refer to postbronchodilator FEV1.

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E. HOW IS COPD DIFFERENTIATED FROM OTHER COMMON CAUSES OFOBSTRUCTIVE LUNG DISEASES IN THE PHILIPPINES, SPECIFICALLYASTHMA & BRONCHIECTASIS?25

In general, most patients presenting with airways obstruction can becategorized into either COPD or Bronchial asthma based on clinical history,physical examination, radiographic findings, pulmonary function test results andon occasion, a therapeutic trial of medication12,13. Bronchial asthma is also achronic inflammatory disorder of the airways involving other kinds ofinflammatory cells. This inflammatory process causes symptoms that are usuallyassociated with widespread but variable airflow obstruction that is oftenreversible. This is in contrast to the progressive and irreversible airwaysobstruction of COPD. It may be difficult to differentiate COPD from asthmaespecially in the elderly who may present with persistent airflow obstruction dueto airway remodeling associated with uncontrolled chronic asthma. Since thetwo conditions are based on distinct disease processes, one must recognize thatboth may be present simultaneously.

Table 4.2 shows the features that may differentiate Bronchial asthma fromCOPD14.

Table 4.214 - Differences Between Asthma and COPDFeatures Asthma COPDOnset at a youngage

Frequently Almost never

Major symptoms Usually episodic Wheezing Breathlessness Non-productive cough Chest tightness

Usually daily Dyspnea with exertion (progressive over time) Productive cough

Triggers AeroallergensOccupational antigensExogenous irritantsExerciseCold airAspirin and NSAID’sReflux esophagitisInfections

Daily activitiesCold airInfections

Smoking history Occasionally present Usually present and of significant durationAllergies Often present Occasionally presentPhysical findings Rhinitis

Pale nasal mucosa Prolonged expiration Wheezing

Diminished intensity of breath sounds inadvanced disease

Pursed lip breathing Signs of right heart failure (distended

jugular veins, right ventricular heave, loudpulmonic component of the secondheart sound, ascites, pedal edema)

Early inspiratory crackles Wheezing

Complete blood Eosinophilia Polycythemia in advanced disease

24

countAlpha-1 antitrypsinlevel

Normal Occasionally low

Spirometry Reduced FEV1

Reduced FEV1/FVC May be normal when

asymptomatic or withtreatment

Reduced FEV1

Reduced FEV1/FVC Reduced values may improve but usually

do not return to normal values even withtreatment

Bronchodilatorresponse inspirometry

Usually presentSpirometry may normalize

May be presentValues usually do not return to normal values

Lung volumes TLC is usually normalRV may be increased

TLC may be normal or increased withemphysematous changesRV is increased

Diffusing capacityfor carbonmonoxide (DLCO)

Normal or increased Reduced with emphysematous changes

Chest radiograph Usually normalOccasionally hyperinflatedlung fields during attacks

Hyperinflation with emphysematous changesBullae may be present

Chest CT scan Usually normal Emphysematous changes, Blebs, bullae,diminished vascularity

Bronchiectasis is characterized by irreversible dilatation of one or more proximaland medium-sized bronchi as a result of destruction of the muscular and elasticsupporting tissues of the bronchial walls15. It is another disease which maypresent itself as chronic airways obstruction. It is common among Filipinos as itcan follow necrotizing pneumonias caused by tubercle bacillus and othermicroorganisms. A high prevalence of asthma in patients with bronchiectasisamong Asians has been reported16.

Localized bronchiectasis is often present in patients with COPD. As a rule,however, bronchiectasis is characterized by dilatation of the airways rather thannarrowing. Cough and sputum production ,frequently purulent, often moresevere on awakening are observed in 90% of all patients with bronchiectasis.Radiographic techniques should be requested to support the diagnosis. Chestradiographs are crucial to document regions of increased markings, cavitiesand atelectasis. When clinical symptoms and plain chest raiographs suggestbronchiectasis, a high resolution computed tomography (HRCT) is the imagingmodality of choice for confirming or ruling out the diagnosis17.

In all subjects with symptoms of COPD, a possible concomitant diagnosis oftuberculosis should be also be considered especially in the Philippines which isendemic for tuberculosis.

F. ONGOING MONITORING AND ASSESSMENT11

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Once COPD is detected and confirmed, ongoing monitoring andassessment should include evaluation of: (1) continued exposure to risk factors,especially tobacco smoke; (2) disease progression and development ofcomplications; (3) pharmacotherapy and other medical treatment; (4)exacerbation history; (5) comorbidities.

Monitor Disease Progression and Development of ComplicationsCOPD is usually a progressive disease. Lung function can be expected to

worsen over time, even with the best available care. Symptoms and objectivemeasures of airflow limitation should be monitored to determine when to modifytherapy and to identify any complications that may develop. As at the initialassessment, follow-up visits should include a physical examination and discussionof symptoms, particularly any new or worsening symptoms. A list of commonlyasked questions during follow-up visits of COPD patients is provided in Appendix2. 11

Pulmonary function. A patient’s decline in lung function is best tracked byperiodic spirometry measurements. Useful information about lung functiondecline is unlikely from spirometry measurements performed more than once ayear. Spirometry should be performed if there is a substantial increase insymptoms or a complication.

Arterial blood gas measurement. Measurement of arterial blood gas tensionsshould be performed in all patients with FEV 1 < 50% predicted or when clinicalsigns of respiratory failure or right heart failure are present. Respiratory failure isindicated by a PaO 2 < 60 mm Hg with or without PaCO 2 > 45 mm Hg in arterialblood gas measurements made while breathing air at sea level. Screeningpatients by pulse oximetry and assessing arterial blood gases in those with anoxygen saturation (SaO 2 ) < 92% may be a useful way of selecting patients forarterial blood gas measurement.

Diagnosis of right heart failure or cor pulmonale. Elevation of the jugular venouspressure and the presence of pitting ankle edema are often the most usefulfindings suggestive of cor pulmonale in clinical practice.Firm diagnosis of cor pulmonale can be made through a number ofinvestigations, including radiography, electrocardiography, echocardiography,radionucleotide scintigraphy, and magnetic resonance imaging. However, all ofthese measures involve inherent inaccuracies of diagnosis.

Hematocrit. Polycythemia can develop in the presence of arterial hypoxemia,especially in continuing smokers. Polycythemia can be identified by hematocrit> 55%.

26

Exercise testing. Several types of tests are available to measure exercisecapacity, and are indicated for preoperative evaluation and pulmonaryrehabilitation.

Monitor Pharmacotherapy and Other Medical Treatment

In order to adjust therapy appropriately as the disease progresses, each follow-up visit should include a discussion of the current therapeutic regimen. Dosagesof various medications, adherence to the regimen, inhaler technique,effectiveness of the current regime at controlling symptoms, and side effects oftreatment should be monitored.

Monitor Exacerbation HistoryDuring periodic assessments, health care workers should question the patientand evaluate any records of exacerbations, both self-treated and those treatedby other health care providers. Frequency, severity, and likely causes ofexacerbations should be evaluated. Increased sputum volume, acutelyworsening dyspnea, and the presence of purulent sputum should be noted.

Monitor ComorbiditiesIn treating patients with COPD, it is important to consider the presence ofconcomitant conditions such as bronchial carcinoma, tuberculosis, sleepapnea, and left heart failure. The appropriate diagnostic tools (chestradiograph, ECG, etc.) should be used whenever symptoms (e.g., hemoptysis)suggest one of these conditions.

Research Recommendations:

1. Develop a prediction model to help diagnose and classify COPD usingvariables that are readily available to the Filipino clinician (e.g., historyand PE findings). Such a model may be more useful and acceptablein a developing country such as ours whereresources (i.e., spirometers and trained operators) are lacking.

2. Undertake studies to validate the GOLD severity classification and theother clinical parameters such as dyspnea and body mass index inpredicting the prognosis and course of COPD among Filipinos.

REFERENCES:

1. American Thoracic Society. Medical section of the American Lung Association. Standards for the Diagnosis andCare of Patients with COPD and Asthma. Am Rev Respir Dis 1987; 136: 225-244.

2. Georgopoulos D, Anthonisen SR. Symptoms and signs of COPD. In: Chermiack NS, ed. Chronic Obstructive

27

Pulmonary Disease. Toronto: WB Saunders; 1991. p.357-63.

3. Medical Research Council. Definition and classification of chronic bronchitis for clinical and epidemiologicalpurposes: a report to the Medical Research Council by their committee on the etiology of Chronic Bronchitis.Lancet 1965; 1: 775-80.

4. Burrows B, Niden AH, Barclay WR, Kasik JE. Chronic obstructive lung disease obstruction. Am Rev Respir Dis1965 ; 665-78.

5. Vermiere P. Definition of COPD. Chapter 1 pp 1-11. In: van Heraarden CLA, Repine JE, Vermiere P, van WeelC (eds): COPD Diagnosis and Treatment. Amsterdam: Excerpta Medica 1996.

6. Kelly CA, Gibson GJ. Relation between FEV1 and peak expiratory flow in patients with COPD. Thorax 1988;43:335-6.

7. Meliton A, Ocampo-Chuatico MR, Punzal P, de Guia T, Blanco-Limpin ME, Lingad R. The use of PEFRmeasurement in obstructive airways diseases. Phil J Chest Dis 1999; 7(1): 21-27.

8. McIvor A, Chapman KR. Diagnosis of COPD and differentiation from asthma. Current Opinion in PulmonaryMedicine 1996; 1(2): 148-154.

9. Bone RC. Bronchiectais. Part G Ch. 6 pp. 1-7. In Bone RC (ed.): Pulmonary and Critical Care Vol 1 MosbyYearbook, St Louis, 1997 Update.

10. Strauss SE, McAlister FA, Sackett DL, Deeks JJ (for the CARE-COAD1 Group). The accuracy of patient history,wheezing, and larngeal measurements in diagnosing obstructive airway disease. JAMA April 2000; 14: 1853-7.

11. Global Initiative for Chronic Obstructive Lung Disease. April 2001; NIH Publication No. 2701B

12. Scott, JA, Mahler DA. Diagnosis of COPD and differentiation from asthma. Curr Opin in Pulm Med 1995;1(2):144-149.

13. American Thoracic Society. Medical section of the American Lung Association. Standards for the diagnosis andcare of patients with COPD and asthma. Am Rev Respir Dis 1987; 136: 225-44.

14. Kaliner M, Lemanski, R. Rhinitis and asthma. JAMA 1992;268:2807-2829.

15. Bone RC. Bronchiectasis. Prt G Chap 6 pp 1-7. Bone RC (ed): Pulmonary and Critical Care Vol 1 Mosby YearBook , St. Louis, 1997 Update.

16. Ip MS, So SY, Lam, WK, et al. High prevalence of asthma in patients with bronchiectasis in Hongkong. Eur Resp J1992; 5(4):418023.

17. Webb WR. High resolution computed tomography of obstructive lung disease. Radiol Clin North Am1994:32(4):745-57.

18 Siafakas NM, Vermiere P, Pride NB. Optimal assessment and management of chronic obstructive pulmonarydisease: A consensus statement of the European Respiratory Society. Eur Resp Journal 1995; 8: 1398-1420.

19. American Thoracic Society-Lung Function Testing: Selection of reference values and interpretative strategies.Am Rev Respir Dis 1991; 144: 1202-18.

20. Sourk RL, Nugent KM. Bronchodilator testing: confidence intervals derived from placebo inhalations. Am RevRespir Dis 1983; 128:153-7.

21. Ries AL. Response to bronchodilators. In : Clausen J, ed. Pulmonary Function Testing: guidelines andcontroversies. New York Academic Press; 1982. p. 215-221.

22. Anthonisen NR, Wright EC. Bronchodilator response in chronic obstructive pulmonary disease. Am Rev Respir Dis1983; 128:153-7.

23. Klein JS, Gamsu G, Webb WR, Golden JA, Muller ML. High Resolution CT diagnosis of emphysema insymptomatic patients with normal chest radiograph and isolated low diffusion capacity. Radiology 1992; 182:817-21.

24. British Thoracic Society. BTS guidelines for the management of COPD. Thorax 1997; 250-252.

28

25. Philippine College of Chest Physicians Council on COPD. Philippine Consensus Report on COPD (1999):Diagnosis and Management.

26. Celli B, Cote C, Marin J, et al. The Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capcity Index inCOPD. New England Journal of Medicine 2004;350:1005-12.

27. Mannino et al. Thorax 2003;58:388-393.

28. Tsounakidou et al. Respiratory Medicine 2004; 98:178-183.

29. Antonelli-Incalzi et al. European Respiratory Journal 2003; 22(3):444-9.

29

V. HOW DO WE MANAGE PATIENTS WITH STABLE COPD?

KEY POINTS:

COPD is a preventable and treatable disease. A holistic approach is needed to address the goals of management of

COPD. Smoking cessation is the single most effective way of reducing the risk of

developing COPD and delaying its progression. Pharmacologic therapy for COPD are mainly for symptom control,

improvement in quality of life, functional capacity and decreasingexacerbation rates and severity as there are no pharmacologic agentsthat have been shown to retard the rate of lung function decline inCOPD.

Bronchodilator use is very important for symptom control in COPD.Inhaled formulations are preferred over oral medications.

Pulmonary rehabilitation is considered an essential component in theholistic treatment of the COPD patient.

Stable COPD refers to the usual daily condition of the COPD patient when he orshe is not having a new respiratory event or sudden worsening of his or hersymptoms. Effective management, therefore, of a COPD patient’s stable stateentails long-term care and aiming for the following goals:

1. delay progression of the disease2. relieve symptoms3. improve exercise capacity4. improve quality of life5. prevent and treat complications6. prevent and treat exacerbations7. reduce mortality

To address these goals in the management of a COPD patient, a holisticapproach is needed. Slowing down of disease progression by avoidance of riskfactors is of primary importance (Evidence A)1-2. Since smoking is the major riskfactor in the development of COPD, smoking cessation is one of the mostimportant strategies to address this goal in the management of COPD. Theother goals in the management of COPD are addressed by pharmacologic andnon-pharmacologic interventions.

A. SMOKING CESSATION

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Smoking cessation is the single most effective way of reducing the risk ofdeveloping COPD and delaying its progression (Evidence A)1,84-85 . Studies haveshown that merely reducing the number of cigarettes smoked does not alter therate of decline in lung function among COPD patients who smoke (EvidenceB)86-88. All smokers, therefore, should be offered the most intensive smokingcessation intervention available. This includes counseling from physicians andother health professionals, pharmacotherapy, self-help and group programs.The employment of a brief (3-minute) counseling to urge a smoker to quit is asimple yet fairly effective method that can be done by all physicians (EvidenceA; see Appendix 3)89-90. Every smoker should be offered this brief counseling atevery visit to a health care provider.

B. PHARMACOLOGIC MANAGEMENT

The goals in instituting pharmacologic therapy for COPD are mainly for symptomcontrol, improvement in quality of life, functional capacity and decreasingexacerbation rates and severity as there are no pharmacologic agents thathave been shown to retard the rate of lung function decline in COPD (EvidenceA)1,38

1. General principles of pharmacologic management

There should be a stepwise increase in treatment depending onsymptoms. (Evidence D).

Treatment response of an individual patient is variable and should bemonitored closely. Regular treatment can be maintained for longperiods of time and adjusted accordingly if & when side effects occur(Evidence D).

Each treatment strategy should be patient-specific and should takeinto consideration not only the severity of symptoms and airflowlimitation but also other factors including the presence of co-morbidities, complications, frequency and severity of exacerbations,and available resources (Evidence D).

2. Pharmacologic agents

Described below are the different classes of pharmacologic agents used inmanaging of stable COPD. Monitoring of clinical and objective measures ofresponse to treatment is encouraged. A complete list of the differentmedications under these classes that are available in the country is found inAppendix 4.

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a. Bronchodilators

Bronchodilators are very important to symptom management in COPD(Evidence A)3-8. The recommended first-line bronchodilators are beta 2-agonistsand/or anticholinergic agents (Evidence A)18-22. The inhaled route is preferredover an oral formulation (Evidence A)6,10. Long-acting inhaled bronchodilatorshave been shown to be more effective and convenient than short-actingbronchodilators, however, these agents are more expensive than the short-acting preparations (Evidence A)27-33. Methylxanthine derivatives arerecommended as second-line drugs (Evidence A)9-14. Depending on the severityof symptoms, regular treatment with one or more bronchodilators with differentmechanisms and durations of action can be given to improve the degree ofbronchodilation for equivalent or lesser side effects (Evidence A)15,17-18,20.

When treatment is given through the inhalational route, COPD patients mayhave problems with effective coordination, thus it is essential to ensure thatinhaler technique is correct and/or spacer devices are utilized (Evidence D)23.Wet nebulizers are not recommended for regular treatment of stable disease(Evidence C)24-25.

Beta2-agonists relax airway smooth muscle by stimulating Beta 2-adrenergicreceptors which results in functional antagonism of bronchoconstriction. Thereare short- and long-acting preparations with durations of action ranging from 4 –6 hours and 8 – 12 hours, respectively7-8,22. Oral and inhaled formulations areavailable, however, the oral preparations have a slower onset and have moresystemic side effects than the inhaled form (Evidence A)6,10. The most frequentside effects of eta 2-agonist treatment include resting sinus tachycardia,somatic tremors, hypokalemia, and mild decrease in arterial oxygenation6, 21.

Anticholinergic medications block the effect of acetylcholine on muscarinic (M2and M3) receptors and may also modify transmission at the pre-synapticjunction15. Short-acting (6 – 8 hours for ipratropium bromide) and long-acting (upto 24 hours for tiotropium bromide) inhaled preparations are currently available.Recent studies have shown superiority of tiotropium over placebo, regularipratropium bromide, and long-acting beta 2-agonists, in improving lungfunction and quality of life over a 6-12 month trial period for mild to severeCOPD (Evidence A)28-33,114. The most frequent side effect with inhaled anti-cholinergic use is dryness of the mouth. The incidence of urinary retention andacute glaucoma with ipratropium bromide nebulization is similar to placebodrug use34.

The mechanisms of action of methylxanthines and xanthine derivatives stillremain controversial, with the non-selective inhibition of phosphodiesterases and

32

stimulation of diaphragmatic contractility among its proposed effects26.Theophyllines have been proven effective in COPD, however, some studieshave demonstrated the lack of additional bronchodilation upon addingtheophylline to other bronchodilators and more side effects with theophyllinecompared to beta 2 agonists and/or anticholinergic agents (Evidence B)9-14.Thus, methylxanthine derivatives like theophylline and doxofylline are stillconsidered as second line drugs in COPD. The side effects associated withtheophylline use are headache, insomnia, nausea, heartburn and the moresevere adverse effects are convulsions, atrial and ventricular arrhythmias thatare dose-related. Doxofylline on the other hand has been noted to be bettertolerated and to have lesser side effects (Evidence B)96-98.

Combination therapy with bronchodilators having different mechanisms anddurations of action may increase the degree of bronchodilation for equivalentor lesser side effects. A number of preparations are currently available, andcombinations of inhaled 2-agonists and anticholinergic agents have beenfound to produce greater and more sustained improvements in FEV1 than eitherdrug alone (Evidence B)15-20. A number of studies have also proposed the use ofan inhaled 2-agonist and corticosteroid combination for the treatment of stableCOPD45,99, however further evidence is being awaited before it can berecommended for routine use.

b. Corticosteroids

There are only specific situations where steroids have a role in COPD.

1. Oral Corticosteroids

With numerous studies documenting lack of benefit and occurrence ofadverse effects, long-term treatment with oral corticosteroids is notrecommended in COPD (Evidence A) 36-44.

2. Inhaled Corticosteroids

Inhaled steroids is recommended for maintenance therapy in any of thefollowing situations:

a. The patient has repeated exacerbations requiring treatment withantibiotics and/or oral steroids (Evidence A) 36-44

b. The patient has advanced COPD (FEV1 < 50% of predicted)(Evidence A) 36-44

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Prolonged treatment with inhaled steroids may decrease the number ofexacerbations and improve health status but does not modify the long-term decline in lung function (Evidence A)37-44. The long-term safety ofinhaled corticosteroids in COPD, however, is not known.

Inhaled steroids combined with long-acting beta 2-agonist is moreeffective than the individual components (Evidence A) 109-113.

c. Immunization

There is strong data to support the efficacy of influenza vaccination in reducingserious illness and even death in COPD patients (Evidence A)54-58. Vaccinederived from the most recent strains should be given every year once the newset of vaccines for the year is available (Evidence D). Pneumococcal vaccinesare also being used, however, data are still insufficient to recommend itsgeneral use in COPD (Evidence B)59-60.

d. Mucolytics/Anti-oxidants

The widespread use of mucolytic agents cannot be recommended on the basisof present evidence (Evidence B)46. Among the anti-oxidants, oral N-acetylcysteine has been shown to decrease the frequency of exacerbations(Evidence B)47-50.

e. Immunomodulators

Based on the results of a recently published local meta-analysis on the efficacyof immunomodulators in COPD, its use is not recommended as it does not causea reduction in the frequency of COPD exacerbations (Evidence B)51.

Anti-leukotriene drugs currently used for bronchial asthma have not been foundto be useful in COPD (Evidence D)100-101.

f. Antibiotics

The use of antibiotics other than for treating infectious exacerbations of COPD isnot recommended (Evidence A)52.

g. Antitussives

The regular use of antitussives in COPD patients is not advisable because coughhas a significant protective role (Evidence D)53.

34

h. Oxygen

Oxygen therapy can be administered in three ways: long-term continuoustherapy, during exercise, and to relieve acute dyspnea. The primary goal ofoxygen therapy is to increase the baseline PaO2 to at least 60 mmHg and/or toproduce arterial oxygen saturation (SaO2) of at least 88-90%.

Long-term oxygen therapy (LTOT) has been shown not only to improve survivalbut also to improve hemodynamics, exercise capacity, lung mechanics, andmental state in patients with COPD and chronic respiratory failure (EvidenceA)61-63

Long-term oxygen therapy is generally indicated in patients with:

PaO2 < 55 mmHg or SaO2 < 88%, with or without hypercapnia (EvidenceA)64-65

PaO2 between 55 mmHg – 60 mmHg, or SaO2 > 89% but with evidence ofpulmonary hypertension, polycythemia (hematocrit > 55%) or peripheraledema suggesting congestive heart failure (Evidence D).

Oxygen therapy should be given during exercise in those patients who alreadymeet the criteria for LTOT and/or to those who develop significant oxygendesaturation during exercise (Evidence C). Oxygen can also be given as forshort periods to control episodes of severe dyspnea (Evidence D).

C. Non-Pharmacologic Management

1. Patient Education

Education is regarded as an essential component of care of COPD patients.Patient education alone has no direct effect on symptoms and does notimprove exercise performance or lung function (Evidence B)66-67. It mayhowever play a role in improving adaptive skills, the ability to cope with illnessand acute exacerbations, and general health status (Evidence D)68. It is also aneffective way to initiate and accomplish smoking cessation, and to initiatediscussions and understanding of advance directives and end-of-life issues(Evidence A)69.

2. Pulmonary Rehabilitation70-83

Pulmonary rehabilitation is considered an essential component in the holistictreatment of the COPD patient regardless of the severity of his lung functionabnormality (Evidence A).

35

Among the proven benefits of pulmonary rehabilitation in COPD are (EvidenceA):

Improvement in exercise capacityReduction in the perceived intensity of breathlessnessImprovement in health-related quality of lifeReduction in the number of hospitalizations and days in the hospitalReduction in the anxiety and depression associated with COPD

Lower extremity exercise training is the necessary component in a pulmonaryrehabilitation program (Evidence A). Strength & endurance training of the upperlimbs improves arm function (Evidence B). Respiratory muscle training may bebeneficial, especially when combined with general exercise training (EvidenceC). Psychosocial intervention is also helpful (Evidence C). The minimum lengthof an effective rehabilitation program is two months; the longer the programcontinues, the more effective the results (Evidence B) 115-117. The benefits ofpulmonary rehabilitation may extend well beyond the immediate period aftertraining (Evidence B).

Pulmonary rehabilitation is currently available in several medical centers (seeAppendix 5 ).

3. Nutrition

Based on a recent meta-analysis, specific nutritional recommendations seem tohave no significant effect on long-term outcomes of COPD patients (EvidenceB)91-92. However, several studies have noted that a low body weight and musclewasting are independent risk factors for mortality in COPD patients (Evidence C)93-95. A balanced diet, nonetheless, is recommended for any COPD patient.

4. Surgery

Surgical intervention for COPD may include bullectomy, lung volume reductionsurgery or lung transplantation. Bullectomy or the removal of large bullae mayimprove gas exchange and reduce dyspnea in carefully selected patients(Evidence C)102.

Lung volume reduction surgery (LVRS) entails resection of some parts of the lungsto reduce hyperinflation, improve the mechanical efficiency of the diaphragmand other respiratory muscles, and improve the elastic recoil pressure of thelung. LVRS has been shown to improve the lung function, exercise capacity andquality of life in some patients (Evidence C). Lung volume reduction surgery,though, is not advised for patients who have a low FEV1 (< 20%) and either

36

homogenous emphysema or a very low carbon monoxide diffusing capacity(Evidence A) 102,108. No local studies on LVRS have been published.

1

D. MANAGEMENT CONTINUUM FOR STABLE COPD

The stepwise holistic approach to treatment based on the severity classification for COPD can be summarized in thisdiagram.

Table 5.1. Diagram on the stepwise holistic approach to treatment of a stable COPD patient.

STAGE

RECOMMENDED TREATMENTAvoidanceof riskfactors &education

Smokingcessation

Influenza &Pneumococcalvaccination

Short-actingBronchodilatoras needed forsymptoms*

Regular use ofsingle orcombinedBronchodilators**

Inhaledsteroids ***

Pulmonaryrehabilitation

Others:

Stage I:MildCOPD

X X X X X

Stage II:ModerateCOPD

X X X X X X

Stage III:SevereCOPD

X X X X X X X Considersurgicaltreatmentoptions

Stage IV:VerySevereCOPD

X X X X X X X Long-termoxygentherapy ifwithpersistenthypoxemia,respiratoryfailure Considersurgicaltreatmentoptions

* Short-acting bronchodilators PRN for symptoms:- Inhaled preferred over oral formulation- Short-acting beta-2 agonists or anticholinergic agents are preferred

2

**Regular use of bronchodilators:- Inhaled preferred over oral formulation.- Single long acting bronchodilator preferred although regular and frequent administration of short-acting

bronchodilators may be used. If symptoms still not controlled, a combination of bronchodilators with differentpharmacologic sites of action can be given to maximize symptom control.

- Long acting anticholinergic agent preferred as the single long acting bronchodilator for regular daily use.*** Inhaled corticosteroids: Recommended only if the patient has:

- significant symptoms- repeated exacerbations- documented lung function response with regular use

3

RESEARCH RECOMMENDATIONS

1. Survey the current use, cost, and relative distribution ofmedical & non-medical resources across the country forCOPD.

2. Determine the cost effectivity of the different pharmacologicand non-pharmacologic interventions for COPD (e.g. regularuse of inhaled versus oral bronchodilator medications,education intervention alone, formal pulmonary rehabilitationprograms, etc.).

3. Perform researches oriented to helping policymakers &agencies formulate, revise & implement laws and regulationsthat can lessen the burden of risk factors for COPD (e.g.Clean Air Act, Framework Convention for Tobacco Control).

4. Confirm the effectivity of novel drugs that may controlsymptoms and prevent the progression of COPD among theFilipino population.

5. Develop indigenous interventions and local herbalmedications that may be as efficacious as presentinterventions & medications for COPD.

6. Validate the effectivity and cost-effectivity of the proposedmanagement continuum for COPD.

REFERENCES:

1. Anthonisen NR, Connett JE, et al. Effects of smoking intervention and the use of an inhaledanticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA 1994;272: 1497–505

2. Scanlon P, Connett J, et al. Smoking cessation and lung function in mild-to-moderate ChronicObstructive Pulmonary Disease. The Lung Health Study. American Journal of Respiratory andCritical Care Medicine 2000; 161:381-390

3. O’Donnell DE, Forkert L, Webb KA. Evaluation of bronchodilator responses in patients with ‘irreversible’emphysema. European Respiratory Journal 2001; 18: 914-20

4. Vathensen AS, Britton JR, et al. High-dose inhaled albuterol in severe chronic airflow limitation.American Review of Respiratory Diseases 1988; 138: 850-5

5. Liesker JJ, Wijkstra PJ, et al. Systematic review of the effects of bronchodilators on exercise capacity inpatients with COPD. Chest 2002; 121(2): 597-608

6. Cazzola M, Calderaro F, et al. Oral bambuterol compared to inhaled salmeterol in patients withpartially reversible chronic obstructive pulmonary disease. European Journal of ClinicalPharmacology 1999; 54: 829-33

7. Sestini P, Renzoni E, et al. Short-acting beta-2 agonists for stable chronic obstructive pulmonarydisease (Cochrane review). In: The Cochrane Library, Issue 2, 2001. Oxford: Update software

8. Appleton S, Smith B, et al. Long-acting beta-2 agonists for chronic obstructive pulmonary disease(Cochrane review). In: The Cochrane Library, Issue 2, 2001. Oxford: Update Software

9. Chrystyn H, Mulley BA, et al. Dose response relation to oral theophylline in severe chronic obstructiveairways disease. British Medical Journal 1988; 297: 1506-10

4

10. Shim CS, Williams MH Jr. Bronchodilator response to oral aminophylline and terbutaline versus aerosolalbuterol in patients with chronic obstructive pulmonary disease. American Journal of Medicine1983; 75: 697-701

11. Murciano D, Auclair MH, et al. A randomized, controlled trial of theophylline in patients with severechronic obstructive pulmonary disease. New England Journal of Medicine 1989; 320: 1521-5

12. McKay SE, Howie CA, et al. Value of theophylline treatment in patients handicapped by chronicobstructive lung disease. Thorax 1993; 48: 227-32

13. Davis B, Brooks G, et al. The efficacy and safety of salmeterol compared to theophylline: meta-analysis of nine controlled studies. Respiratory Medicine 1998; 92: 256-63

14. Canizares LL, Fernandez OU, et al. A meta-analysis on the additive effect of oral theophylline onbeta-agonists and/or anticholinergic agents in patients with chronic obstructive pulmonary disease.Philippine Journal of Chest Diseases 1995; 3: 114-9

15. COMBIVENT inhalational aerosol study group. In chronic obstructive pulmonary disease, acombination of ipratropium and albuterol is more effective than either agent alone. An 85-daymulticenter trial. Chest 1994; 105: 1411-9

16. Gross NJ, Petty TL, et al. Dose response to ipratropium as a nebulized solution in patients with chronicobstructive pulmonary disease. A three-center study. American Review of Respiratory Diseases1989; 139: 1188-91

17. Guyatt GH, Townsend M, et al. Bronchodilators in chronic airflow limitation. Effects on airwayfunction, exercise capacity and quality of life. American Review of Respiratory Diseases 1987; 135:1069-74

18. Ikeda A, Nishimura K, et al. Bronchodilating effects of combined therapy with clinical dosages ofipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone.Chest 1995; 107: 401-5

19. The COMBIVENT inhalational solution study group. Routine nebulized ipratropium and albuteroltogether are better than either alone in COPD. Chest 1997; 112: 1514-21

20. Gross N, Tashkin D, et al. Inhalation by nebulization of albuterol-ipratropium combination is superior toeither agent alone in the treatment of chronic obstructive pulmonary disease. Dey combinationsolution study group. Respiration 1998; 65: 354-62

21. Khoukaz G, Gross NJ. Effects of salmeterol on arterial blood gases in patients with stable chronicobstructive pulmonary disease. Comparison with albuterol and ipratropium. American Journal ofRespiratory Critical Care Medicine. 1999; 160: 1028-30

22. Boyd G, Morice AH, et al. An evaluation of salmeterol in the treatment of chronic obstructivepulmonary disease. European Respiratory Journal 1997; 10: 815-21

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24. Jenkins SC, Heaton RW, et al. Comparison of domiciliary nebulized salbutamol and salbutamol from ametered-dose inhaler in stable chronic airflow limitation. Chest 1987; 91: 804-7

25. O’Driscoll BR, Kay EA, et al. A long-term prospective assessment of home nebulizer treatment.Respiratory Medicine 1992; 86: 317-25

26. Aubier M. Pharmacotherapy of respiratory muscles. Clinics in Chest Medicine 1988; 9: 311-24

27. Van Noord JA, De Munck DR, et al. Long-term treatment of chronic obstructive pulmonary diseasewith salmeterol and the additive effect of ipratropium. European Respiratory Journal 2000; 15: 878-85

5

28. Donohue JF, Van Noord JA, et al. A 6-month, placebo-controlled study comparing lung function andhealth status changes in COPD patients treated with tiotropium or salmeterol. Chest 2002 Jul; 122(1);47-55

29. Vincken W, Van Noord JA, et al. Improved health outcomes in patients with COPD during 1 yeartreatment with tiotropium. European Respiratory Journal 2002 Feb; 19(2): 209-16

30. Casaburi R, Mahler DA, et al. A long-term evaluation of once-daily inhaled tiotropium in chronicobstructive pulmonary disease. European Respiratory Journal 2002 Feb; 19(2): 217-24

31. Casaburi R, Briggs Dd, et al. The spirometric efficacy of once-daily dosing with tiotropium in stableCOPD: A 13-week multi-center trial. The US Tiotropium Study Group. Chest 2000 Nov; 118(5): 1294-302

32. Littner MR, Ilowite JS, et al. Long-acting bronchodilation with once-daily dosing of tiotropium (Spiriva)in stable chronic obstructive pulmonary disease. American Journal of Respiratory and Critical CareMedicine. 2000 Apr; 161(4 Pt 1): 1136-42

33. Van Noord JA, Bantje TA, et al. A randomized controlled comparison of tiotropium and ipratropium inthe treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group. Thorax2000 Apr; 55(4): 289-94

34. Taylor J, Kotch A, et al. Ipratropium bromide HFA study group: Ipratropium bromide hydrofluoroalkaneinhalation aerosol is safe and effective in patients with COPD. Chest 2001 Oct; 120(4): 1253-61

35. Tashkin DP, Bleecker E et al. Results of a multicenter study of nebulized inhalant bronchodilatorsolutions. American Journal of Medicine 1996; 100: 62-9s

36. Senderovitz T, Vestbo J et al. Steroid reversibility test followed by inhaled budesonide or placebo inoutpatients with stable chronic obstructive pulmonary disease. The Danish society of respiratorymedicine. Respiratory Medicine 1999; 93: 715-8

37. Callahan CM, Dittus RS et al. Oral corticosteroid therapy for patients with stable chronic obstructivepulmonary disease. A meta-analysis. Annals of Internal Medicine 1991; 114: 216-23

38. The lung health study research group. Effect of inhaled triamcinolone on the decline in pulmonaryfunction in chronic obstructive pulmonary disease. New England Journal of Medicine 2000; 343:1902-9

39. Pauwels RA, Lofdahl CG, et al. Long-term treatment with inhaled budesonide in persons with mildchronic obstructive pulmonary disease who continue smoking. European Respiratory Society Studyon Chronic Obstructive Pulmonary Disease. New England Journal of Medicine 1999; 340: 1948-53

40. Vestbo J, Sorensen T, et al. Long-term effect of inhaled budesonide in mild and moderate chronicobstructive pulmonary disease: a randomized controlled trial. Lancet 1999; 353: 1819-23

41. Burge PS, Calverley PM, et al. Randomized, double blind, placebo controlled study of fluticasoneproprionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDEtrial. British Medical Journal 2000; 320: 1297-303

42. Paggiaro PL, Dahle R et al. Multi-centre randomized placebo-controlled trial of inhaled fluticasonepropionate in patients with chronic obstructive pulmonary disease. Lancet 1998; 351: 773-80

43. Van der Valk P, Monninkhof E, et al. Effect of discontinuation of inhaled corticosteroids in patients withchronic obstructive pulmonary disease: The COPE study. American Journal of Respiratory andCritical Care Medicine. 2002 Nov; 166(10): 1358-63

44. Van Grunsven RM, Van Schayck CP, et al. Long term effects of inhaled corticosteroids in chronicobstructive pulmonary disease: A meta-analysis. Thorax. 1999 Jan; 54(1): 7-14

45. Mahler DA, Wire P, et al. Effectiveness of fluticasone proprionate and salmeterol combinationdelivered via the diskus device in the treatment of chronic obstructive pulmonary disease.American Journal of Respiratory and Critical Care Medicine. 2002 Oct; 166(8): 1084-91

46. Poole PJ, Black PN et al. Mucolytic agents for chronic obstructive pulmonary disease (Cochranereview). In: The Cochrane Library, Issue 2, 2001. Oxford: Update Software

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47. Poole PJ, Black PN. Oral N-acetylcysteine and exacerbation rates in patients with chronic bronchitisand severe airways obstruction. British Thoracic Society Research Committee. Thorax 1985; 40: 832-5

48. Boman G, Backer S, et al. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: Reportof a trial organized by the Swedish Society for Pulmonary Diseases. European Journal of RespiratoryDiseases. 1983; 64: 415-15

49. Pela R, Calcagni AM, et al. N-acetylcysteine reduces the exacerbation rate in patients with moderateto severe COPD. Respiration. 1999 Nov-Dec; 66(6): 495-500

50. Stey C, Steurer J, et al. The effect of oral N-acetylcysteine in chronic bronchitis: A quantitativesystematic review. European Respiratory Journal. 2000; 16: 253-62

51. Villaroman ML, Manuel I, et al. Immunomodulators in preventing recurrent respiratory tract infections(RRTI): A meta-analysis. Philippine Journal of Internal Medicine 2001; 39: 193-200

52. Isada CM, Stoller JK. Chronic Bronchitis: The role of antibiotics. In: Neiderman MS, Sarosi GA et al.Respiratory Infections: A scientific basis for management. London: WB Saunders; 1994 p. 621-33

53. Irwin RS, Boulet LP, et al. Managing cough as a defense mechanism and as a symptom. A consensuspanel report of the American College of Chest Physicians. Chest 1998; 114: 133-81s

54. Nichol KL, Margolis KL, et al. The efficacy and cost effectiveness of vaccination against influenzaamong elderly persons living in the community. New England Journal of Medicine 1994; 331: 778-84

55. Edwards KM, Dupont WD, et al. A randomized controlled trial of cold-adapted and inactivatedvaccines for the prevention of influenza A disease. Journal of Infectious Disease 1994; 169: 68-76

56. Poole PJ, Chacko E, et al. Influenza vaccine for patients with chronic obstructive pulmonary diseases(Cochrane review). In: The Cochrane Database of Systematic Reviews, Issue 4, 2002. Oxford:Update Software

57. Caseja M, Balanag V. Flu vaccine as protection against acute exacerbation of COPD. PhilippineJournal of Chest Diseases. 1999; 13(1): 23-6

58. Arreza L, Fernandez LL et al. The effect of Influenza vaccination on the Quality of Life in patients withchronic lung disease. (Abstract). European Respiratory Journal 2000 16(S31):47s

59. Davis AL, Aranda CP, et al. Pneumococcal infection and immunologic response to pneumococcalvaccine in chronic obstructive pulmonary disease. A pilot study. Chest 1987; 92: 204-12

60. Jonsson S, Vidarsson G, et al. Vaccination of COPD patients with a pneumococcus type 6B tetanustoxoid conjugate vaccine. European Respiratory Journal. 2002 Oct; 20(4): 813-8

61. Tarpy SP, Celli BR. Long-term oxygen therapy. New England Journal of Medicine 1995; 333: 710-14

62. Petty Tl. Supportive therapy in COPD. Chest 1998; 113: 256-62s

63. Aniceto E, Francisco N. Survival of patients in the LCP Home Oxygen Program: A Preliminary Report.Philippine Journal of Chest Diseases 2000; 7: 46-51

64. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemicchronic obstructive lung disease: A clinical trial. Annals of Internal Medicine. 1980; 93: 391-8

65. Medical Research Council Working Party. Long-term domiciliary oxygen therapy in chronic hypoxiccor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981; 1: 681-6

66. Janelli LM, Scherer YK, et al. Can a pulmonary health teaching program alter patients’ ability to copewith COPD? Rehabilitation Nursing 1991; 16: 199-202

67. Ashikaga T, Vacek PM, et al. Evaluation of a community-based education program for individualswith chronic obstructive pulmonary disease. Journal of Rehabilitation 1980; 46: 23-7

68. Celli BR. Pulmonary rehabilitation in patients with COPD. American Journal of Respiratory and CriticalCare Medicine 1995; 152: 861-4

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69. Heffner JE, Fahy B, et al. Outcomes of advance directive education of pulmonary rehabilitationpatients. American Journal of Respiratory and Critical Care Medicine 1997; 155: 1055-9

70. ACCP/AACVPR Pulmonary Rehabilitation Guidelines Panel, American College of Chest Physicians andAmerican Association of Cardiovascular and Pulmonary Rehabilitation. Pulmonary Rehabilitation:joint ACCP/AACVPR evidence-based guidelines. Chest 1997; 112: 1363-96

71. Morgan, M. The prediction of benefit from pulmonary rehabilitation: Setting, training intensity and theeffect of selection of disability. European Respiratory Journal. 1998; 12: 363-9

72. Goldstein RS, Gort EH et al. Randomized controlled trial of pulmonary rehabilitation. Lancet 1994; 344:1394-8

73. Ries AL, Kaplan RM, et al. Effects of pulmonary rehabilitation on physiologic and psychosocialoutcomes in patients with chronic obstructive pulmonary disease. Annals of Internal Medicine. 1995Jun; 122(11): 823-32

74. Punzal PA, Ries AL, et al. Maximum intensity exercise training in patients with chronic obstructivepulmonary disease. Chest. 1991 Sep; 100(3): 618-23

75. Santos E, Centina P, et al. The COPD comprehensive pulmonary rehabilitation program: More hopefor the COPD patient. Philippine Journal of Internal Medicine. 1990; 28: 309-21

76. Blanco ME, Koh A, et al. Pulmonary rehabilitation – A multi-disciplinary program for Filipino patients.Philippine Heart Center Journal. 1995; 2: 32-7

77. Fernandez L, Dantes R, et al. A randomized controlled trial on the long-term effects of mulitipleexposure to pulmonary rehabilitation on stable COPD patients (abstract). Chest. 1999; 116(4, S2):276s

78. Foglio K, Bianchi L et al. Is it really useful to repeat outpatient pulmonary rehabilitation programs inpatients with chronic airway obstruction? A 2-year controlled study. Chest. 2001 Jun; 119(6): 1696-704

79. Fernandez LC, Benedicto JP, et al. A randomized controlled trial on the long-term effects of multipleexposures to pulmonary rehabilitation on stable COPD patients. Philippine Journal of ChestDiseases 2000; 7: 40-45

80. Lox CL, Freehill AJ, et al. Impact of pulmonary rehabilitation on self-efficacy, quality of life andexercise tolerance. Rehabilitation Psychology 1999; 44:208

81. Lacasse Y, Wong E et al. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonarydisease. Lancet 1996; 348: 1115-9

82. O’Donnell DE, McGuire M, et al. The impact of exercise reconditioning on breathlessness in severechronic airflow limitation. American Journal of Respiratory and Critical Care Medicine 1995; 152:2005-13

83. Wijkstra PJ, Ten Vergert EM, et al. Long-term benefits of rehabilitation at home on quality of life andexercise tolerance in patients with chronic obstructive pulmonary disease. Thorax 1995; 50: 824-8

84. World Health Organization. Tobacco Free Initiative: Policies for Public Health. Geneva: World HealthOrganization: 1999

85. Fiore MC, Bailey WC, et al. Smoking Cessation: Information for specialists. Rockville, MD: USDepartment of Health and Human Services, Public Health Service, Agency for Health Care Policyand Research and Centers for Disease Control and Prevention; 1996.

86. Reyes RG, Fernandez, LC. Smoking cessation intervention in a tertiary hospital: The UP-PhilippineGeneral Hospital Stop Smoking Program Experience. Philippine Journal of Internal Medicine 2001;39: 337-41

87. Baillie AJ, Mattick RP, et al. Meta-analytic review of the efficacy of smoking cessation interventions.Drug and Alcohol Review 1994; 13: 157-70

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88. Kottke TE, Battista RN, et al. Attributes of successful smoking cessation interventions in medicalpractice. A meta-analysis of 39 controlled trials. JAMA 1988; 259: 2888-9

89. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and ConsortiumRepresentatives. A clinical practice guideline for treating tobacco use and dependence. JAMA2000; 283: 244-54

90. American Medical Association. Guidelines for the diagnosis and treatment of nicotine dependence:how to help patients stop smoking. Washington, DC: American Medical Association; 1994

91. Ferreira I, Brooks D, et al. Nutritional intervention in COPD: A systematic overview. Chest. 2001; 119: 353-63

92. Ferreira IM, Brooke D, et al. Nutritional supplementation for stable COPD (Cochrane review). In: TheCochrane Library, Issue 2, 2001. Oxford: Update Software

93. Gray-Donald K, Gibbons L, et al. Nutritional status and mortality in chronic obstructive pulmonarydisease. American Journal of Respiratory and Critical Care Medicine. 1996; 153: 961-6

94. Creutzberg EC, Annemie M, et al. Characterization of nonresponse to high caloric oral nutritionaltherapy in depleted patients with chronic obstructive pulmonary disease. American Journal ofRespiratory and Critical Care Medicine 2000 Mar; 161(3): 745-52

95. Ferreira I, Verreschi I, et al. The influence of 6 months of anabolic steroids on body mass andrespiratory muscles in undernourished COPD patients. Chest. 1998; 114: 19-28

96. Villani F, De Maria P, et al. Oral doxofylline in patients with chronic obstructive pulmonary disease.International Journal of Clinical Pharmacology and Therapeutics. 1997; 35(3): 107-11

97. Melillo G, Balzano G, et al. Treatment of reversible chronic airways obstruction with doxofyllinecompared with slow-release theophylline: A double-blind, randomized, multi-centre trial.International Journal of Clinical Pharmacology and Research. 1989; 9(6): 397-405

98. Dini FL, Pasini G, et al. Methylxanthine drug therapy in chronic heart failure associated withhypoxemia: Double-blind placebo-controlled clinical trial of doxofylline versus theophylline andbamifylline. International Journal of Clinical Pharmacology and Research. 1993; 13(6): 305-16

99. Cazzola M, Di Lorenzo G, et al. Additive effects of Salmeterol and Fluticasone or Theophylline inCOPD. Chest. 2000; 118(6): 1576-81

100. Kilfeather S. 5-lipoxygenase inhibitors for the treatment of COPD. Chest 2002; 121: 197s-200s

101. Barnes PJ. Novel approaches and targets for treatment of chronic obstructive pulmonary diseases.American Journal of Respiratory and Critical Care Medicine 1999 Nov; 160(5): S72-79

102. Mehran RJ, Deslauriers J. Indications for surgery and patient work-up for bullectomy. Chest SurgicalClinics of North America. 1995; 5: 717-34

103. Martinez FJ, de Oca MM, et al. Lung volume reduction improves dyspnea, dynamic hyperinflation,and respiratory muscle function. American Journal of Respiratory and Critical Care Medicine 1999;155: 1984-90

104. Fessler HE, Permutt S. Lung volume reduction surgery and airflow limitation. American Journal ofRespiratory and Critical Care Medicine 1998; 157: 715-22

105. Gelb AF, McKenna RJ, et al. Lung function 4 years after lung volume reduction surgery foremphysema. Chest 1999; 116: 1608-15

106. Cooper JD, Patterson GA, et al. Results of 150 consecutive bilateral lung volume reduction proceduresin patients with severe emphysema. Journal of Thoracic and Cardiovascular Surgery. 1996; 112:1319-29

107. Banditt JO, Albert RK. Surgical options for patients with advanced emphysema. Clinics of ChestMedicine 1997; 18: 577-83

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108. Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reductionsurgery with medical therapy for severe emphysema. New England Journal of Medicine2003;348(21):2059-73.

109. Mahler D, Wire P, Horstman D, et al. Effectiveness of fluticasone propionate and salmeterolcombination delivered via the Diskus device in the treatment of COPD. Am J Respir Crit Care Med2002;166(8):1084-91.

110. Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment ofCOPD: a randomized controlled trial. Lancet 2003; 361:449-56.

111. Hanania NA, Darken P, Horstman D, et al. The efficacy and safety of fluticasone prionate(250microg)/salmeterol 0 microg) combined in the Diskus inhaler for the treatment of COPD. Chest2003;124(3):834-43.

112. Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of budesonide/formterol in themanagement of COPD. European Respiratory J 2003; 21:74-81.

113. Calverley P, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol inCOPD. European Respiratory Journal 2003;22(6):912-9.

114. de Guia, Punzal, Canizares-Fernandez, Dantes, Salonga, Aquino, Ayuyao, Trinidad. Evaluation ofResponse of Filipino patients to Tiotropium (EVEREST). (Abstract) American Journal of Respiratory &Critical Care Medicine April 2004, 169(7):A611.

115. Behnke et al Respir Med 2000; 94:1184-91116. Finnerty et al Chest 2001;119:1705-10117. Green et al Thorax 2001;56:143-5

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VI. HOW DO WE MANAGE A COPD PATIENT IN ACUTEEXACERBATION?

KEY POINTS:

Acute exacerbation is a new respiratory event or complicationsuperimposed upon established COPD.

The most common causes of a COPD exacerbation are infection ofthe tracheobronchial tree and air pollution.

Acute exacerbation can be treated at home or in the hospitalusing step-wise approaches.

Increase in bronchodilator therapy, use of systemicglucocorticosteroids as indicated, controlled oxygen therapy anduse of antibiotics when indicated, and vigilant monitoring of theCOPD patient are the common therapeutic interventions during anacute exacerbation.

A. DEFINITION OF COPD IN ACUTE EXACERBATION

It is recognized that an acute exacerbation of COPD is difficult to defineand that its pathogenesis is poorly understood.59 The difficulties inobtaining a standard definition for an exacerbation stem from two mainissues: fluctuation of symptoms and the role of co-morbid conditions.

As a generalization however, most published definitions characterize anacute exacerbation as a new respiratory event or complicationsuperimposed upon established COPD. Acute exacerbation of COPD ispresented as the worsening of the previous stable situation.1-5 Mostdefinitions embrace some combination of the following three clinicalfindings: worsening of dyspnea, increase in sputum purulence, andincrease in sputum volume.

In COPD exacerbations, there is a sustained worsening of the patient’scondition from the stable state and beyond normal day- to-dayvariations, that is acute in onset and necessitates a change in regularmedications for COPD.3

Conditions that may mimic an acute exacerbation include pneumonia,congestive heart failure, pneumothorax, pleural effusion, pulmonaryembolism, and arrhythmia.2

11

B. COMMON CAUSES OF ACUTE EXACERBATION OF COPD

The most common causes of an exacerbation are infection of thetracheobronchial tree and air pollution, but the cause of about one-thirdof severe exacerbations cannot be identified (Evidence B). 2

Fig. 5.1. Common Causes of Acute Exacerbations ofCOPD2

Primary Tracheobronchial infection Air pollution

Secondary Pneumonia Pneumothorax Pulmonary embolism Right and/or left heart failure or arrhythmias Inappropriate use of sedatives, narcotics, B-

blocking agents Rib fractures/chest trauma

12

C. SEVERITY CLASSIFICATION OF COPD IN ACUTE EXACERBATION

Unlike the staging systems for stable COPD, there are no standardized andvalidated grading systems for severity of an acute exacerbation.Assessment of the severity of an acute exacerbation is based on thepatient’s medical history before the exacerbation, symptoms, physicalexamination, lung function tests, arterial blood gas measurements, andother laboratory tests.2

Fig 5.2. Medical History and Signs of Severity of AcuteExacerbations of COPD 2, 6-12

Medical History Duration of worsening or

new symptoms Number of previous

episodes(exacerbations/hospitalizations)

Present treatment regimen

Signs of Severity Use of accessory

respiratory muscles Paradoxical chest

wall movements Worsening or new

onset centralcyanosis

Development ofperipheral edema

Hemodynamicinstability

Signs of right heartfailure

Reduced alertness

13

D. HOME MANAGEMENT

Acute exacerbation can be treated at home when patients present withthe following clinical conditions: (a) mild to moderate breathlessness, (b)normal level of consciousness, and (c) generally good condition and levelof activity (Evidence C)2.

The algorithm reported in Fig 5.3 may assist in the management of anacute exacerbation at home; a stepwise therapeutic approach isrecommended.2

Fig. 5.3. Algorithm for the Management of an Acute Exacerbation ofCOPD at Home

Initiate or increase bronchodilator therapyConsider antibiotics

Reassess within hours

No resolution or improvement

Add oral corticosteroids

Reassess within hours

Worsening of signs/symptoms

Refer to hospital

Resolution or improvementof signs & symptoms

Continue managementStep down when possible

Review Long- term management

14

1. Bronchodilator therapy

Home management of COPD exacerbations involves increasing the doseand/or frequency of existing bronchodilator therapy (Evidence A). If notalready used, an anticholinergic can be added until symptoms improve.2

2. Antibiotics

Antibiotic use is recommended if the patient has evidence of bacterialinfection such as fever, increased sputum volume and purulence,leukocytosis, or change in the chest radiograph (Evidence B).22-27 Theantibiotic of choice should reflect known local pattern of resistance.

3. Glucocorticosteroids

Systemic glucorticosteroids are beneficial in the management of COPD inacute exacerbation. They hasten recovery and restore lung function morequickly (Evidence A).19-21, 28, 29 Short course systemic corticosteroids shouldbe considered in patients with acute exacerbation who are unresponsiveto aggressive inhaled bronchodilator therapy or for patients whosebaseline FEV1 < 50% predicted. A dose of 40 mg prednisolone per day for10 days is recommended (Evidence D).2

E. HOSPITAL MANAGEMENT

The risk of dying from an acute exacerbation of COPD is closely related tothe development of respiratory acidosis, the presence of significantcomorbidities, and the need for ventilatory support.13 Patients with theseconditions and those with severe underlying COPD often requirehospitalization.

15

Figure 5.4. Algorithm for the Management of an Acute Exacerbation ofCOPD in the Hospital

Initial ManagementDiagnostics:Chest Xray, ABGTherapeutics:

Controlled oxygen therapyBronchodilatorsOral or IV glucocorticosteroidsConsider Antibiotics

Patients with COPD in acuteexacerbation presenting at theEmergency Room/Hospital

ICU admissionindicated?

Admit to ICUYes

With initialindications for

Hospital admission?

Yes Admit towards

No

Yes Admit towards or ICU

Worsening or noimprovement of symptoms

to initial managementwithin 60 mins?

No

Improvementsustained for 4 hours?

Continue presenttreatmentReassess after 4 hours

Yes Consider hometreatment

No

Admit towards or ICU

No

16

1. Initial Management of exacerbations of COPD in the EmergencyDepartment or the Hospital

a. Assess severity of symptoms, blood gases, chest x-ray31

b. Administer controlled oxygen therapy if the patient is hypoxemic.Repeat arterial blood gas measurement 30 minutes after todetermine adequacy of oxygen therapy (PaO2 > 60 mmHg, or O2saturation > 90%). Venturi masks are more accurate sources ofcontrolled oxygen than are nasal prongs.

c. Bronchodilator therapy:31

Increase doses or frequency of inhaled bronchodilators Combine beta-2 agonists and anticholinergics32,33

Use spacers or nebulizers Consider adding intravenous aminophylline, if needed 34,35

Inhaled short-acting Beta-2 agonists and anticholinergic agents, asbronchodilators, have similar effects on spirometry and a greatereffect than all parenterally administered bronchodilators (that is,parenteral methyxanthines and sympathomimetics) (Evidence A).

Both inhaled beta-adrenergic agonists and anticholinergic agentscan improve airflow during acute exacerbations of COPD.31,60-62

Beta-adrenergic agonists have not been shown to be superior toanticholinergic agents. 31,60-63 Factors such as time to peak effect(which is slightly more rapid with beta-adrenergic agonists) and thefrequency of adverse effects (which are generally fewer and milderwith ipratropium bromide) may influence the choice of agents for agiven patient.

A recent meta-analysis61 supports a strategy of initial use of aninhaled anticholinergic agent, with subsequent addition of a beta-adrenergic agonist only if it is needed despite the use of maximaldoses of the anticholinergic medication (Evidence B).

Equivalent bronchodilation appears to be achieved with the use ofmetered-dose inhalers or nebulizers (Evidence A).

In more severe exacerbation, addition of an oral or intravenousmethylxanthine to the treatment can be considered. 2, 34, 35, 60, 63-66

(Evidence B). However, close monitoring of serum theophylline isrecommended to avoid the side effects of these drugs2.

17

d. Start oral or intravenous glucocorticosteroids19-21, 31

Oral or intravenous glucocorticosteroids are recommended as anaddition to bronchodilator therapy in the hospital management ofacute exacerbation of COPD (Evidence A). Thirty to 40 mg of oralprednisone daily for 10 to 14 days is a reasonable compromisebetween efficacy and safety.2 (Evidence D). The optimal durationof corticosteroid therapy for an acute exacerbation of COPDremains uncertain, but recent data support a course of 5-10 days.20,

67,68 Inhaled steroids are not appropriate in the treatment of acuteexacerbation if COPD.

e. Consider antibiotic therapy

Consider starting antibiotics when there are signs of possiblebacterial infection. Antibiotics may be given by the oral and,occasionally, intravenous route.18

Antibiotics appear to be most useful in patients with severeexacerbation.

f. Consider noninvasive mechanical ventilation.31, 36-44

g. At all times:

Monitor fluid balance and nutrition45, 46

Consider subcutaneous heparin Identify and treat associated conditions (e.g. heart failure,

arrhythmias) Closely monitor the condition of the patient

2. The inclusion criteria for admission in the Intensive Care Unit (ICU)are:47

a. Severe dyspnea that responds inadequately to initialemergency therapy

b. Confusion, lethargy, comac. Persistent or worsening hypoxemia (PaO2 < 50 mmHg),

and/or severe/worsening hypercapnia (PaCO2 > 70 mmHg),and/or severe/worsening respiratory acidosis (pH < 7.30)despite supplemental oxygen and non-invasive positivepressure ventilation (NIPPV).

18

3. The following are indications for hospital assessment or admission foracute exacerbations of COPD (Evidence D): 6, 10, 13-17

Marked increase in intensity of symptoms (severebreathlessness, poor and deteriorating condition or level ofactivity, reduced alertness)

Severe background of COPD New onset cyanosis and peripheral edema Failure of the patient in exacerbation to respond to initial

medical management Significant co-morbidities Newly occurring arrhythmias Diagnostic uncertainty Older age Insufficient home support

F. INTENSIVE CARE UNIT MANAGEMENT

In life threatening exacerbations of COPD, patients should be admitted tothe ICU immediately for ventilatory support.

1. Candidates for NIPPV* during acute exacerbation37

NIPPV increases pH, reduces PaCO2, reduces the severity ofbreathlessness in the first 4 hours of treatment, and decreases the lengthof hospital stay (Evidence A).36-44

A. Selection criteria (at least 2 should be present):1. Moderate to severe dyspnea with use of accessory muscles

and paradoxical abdominal motion2. Moderate to severe acidosis (pH 7.30-7.35) and hypercapnia

(PaCO2 > 45-60 mmHg)3. Respiratory frequency > 25 breaths per minute

B. Exclusion criteria (any may be present):1. Respiratory arrest2. Cardiovascular instability (hypotension, arrhythmias,

myocardial infarction)3. Somnolence, impaired mental status, uncooperative patient4. High aspiration risk, viscous or copious secretions5. Recent facial or gastroesophageal surgery6. Craniofacial trauma, fixed nasopharyngeal abnormalities7. Burns8. Extreme obesity

19

2. Indications for starting invasive mechanical ventilation during acuteexacerbation

The indications are:47, 48

a. severe dyspnea with use of accessory muscles andparadoxical abdominal motion

b. respiratory frequency > 35 breaths per minutec. life-threatening hypoxemia (PaO2 < 40 mmHg or PaO2/FiO2 <

200)d. severe acidosis (pH < 7.25) and hypercapnia (PaCO2 > 60

mmHg)e. respiratory arrestf. somnolence, impaired mental statusg. cardiovascular complications (hypotension, shock, heart

failure)h. Other complications (metabolic abnormalities, sepsis,

pneumonia, pulmonary embolism, barotraumas, massivepleural effusion)

i. NIPPV failure or with exclusion criteria

G. HOSPITAL DISCHARGE AND FOLLOW-UP

1. Discharge criteria:17, 49-53

a. inhaled beta 2 agonist therapy is required no more frequently thanevery 4 hours

b. patient, if previously ambulatory, is able to walk across the room.c. patient is able to eat and sleep without frequent awakening by

dyspnead. patient has been clinically stable for 12-24 hourse. arterial blood gases have been stable for 12-24 hoursf. patient (or home caregiver) fully understands correct use of

medications.g. Follow-up and home care arrangements have been completed

(e.g. visiting nurse, oxygen therapy, meal provisions)h. Patient, family, and physician are confident that the patient can

manage successfully at home.

2. Follow-up assessment

Ideally, the patient should be followed at 4-6 weeks after discharge. Thefollowing components are assessed:54

20

a. ability to cope in the usual environmentb. measurement of FEV1c. reassessment of inhaler techniqued. understanding of recommended treatment regimene. need for long-term oxygen therapy (for patients with severe

COPD).

H. SPECIALIST REFERRAL

The following conditions or events in COPD patient may warrant referral toa pulmonary medicine specialist for further management:

REASON PURPOSEThere is diagnostic uncertainty Confirm diagnosis and optimize

therapySuspected severe COPD Confirm diagnosis and optimize

therapyThe patient requests a secondopinion

Confirm diagnosis and optimizetherapy

Onset of cor pulmonale Confirm diagnosis and optimizetherapy

Assessment for oxygen therapy Optimize therapy and measureblood gases

Assessment for long-term nebulisertherapy

Optimize therapy and excludeinappropriate prescriptions

Assessment for oral corticosteroidtherapy

Justify need for long-term treatmentor supervise withdrawal

Bullous lung disease Identify candidates for surgeryA rapid decline in FEV1 Encourage early interventionAssessment for pulmonaryrehabilitation

Identify candidates for pulmonaryrehabilitation

Assessment for lung volumereduction surgery

Identify candidates for surgery

Assessment for lung transplantation Identify candidates for surgeryDysfunctional breathing Confirm diagnosis, optimize

pharmacotherapy and accessother therapists

Aged under 40 years or a familyhistory of alpha-1 antitrypsindeficiency

Identify alpha-1 antitrypsindeficiency, consider therapy andscreen family

Uncertain diagnosis Make a diagnosisSymptoms disproportionate to lungfunction deficit

Look for other explanations

21

Frequent infections Exclude bronchiectasis; optimizetherapy and preventive measures

Hemoptysis Exclude carcinoma of thebronchus, tuberculosis and otherconditions

Preoperative clearance &perioperative management forcomplicated or extensive surgery

Optimize perioperativemanagement and preventperioperative complications

I. ETHICAL ISSUES

All patients with COPD developing acute respiratory failure should beconsidered for intubation and mechanical ventilation. However, inpatients who have poor baseline function, marginal nutritional status,severely restricted activity levels and inexorable deterioration of their late-stage pulmonary dysfunction, the decision to forego intubation should bereferred to a Bioethics Task Force.

It is also recommended in our setting that the following be carried out:1. Creation of a Bioethics Task Force created from the different local

medical societies to set guidelines on the withholding andwithdrawal of mechanical ventilatory support based on ethicalprinciples.

2. Establishment of an ethics committee in hospitals to help physiciansidentify, analyze and resolve ethical problems in patient care.

3. Development by medical societies of a consensus on the definitionof quality of life to guide clinical management in the institution oflife-sustaining therapy.

RESEARCH RECOMMENDATIONS:

1. Develop a reproducible, transportable definition of “acuteexacerbation” in order to provide more consistent and transparentinclusion and exclusion criteria for clinical trials studying this entity.

2. Conduct randomized placebo controlled trials of the newer broad-spectrum antibiotics.

3. Research on optimal dose and duration of systemic corticosteroidsin acute exacerbation.

4. Research on strategies aimed at preventing and abortingexacerbations.

5. Research on the role of environmental factors and infectious agentsin exacerbations.

22

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11. Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, et al. Time course and recovery ofexacerbations in patients with chronic obstructive pulmonary disease. American Journal ofRespiratory and Critical Care Medicine May 2000; 161(5): 1608-1613.

12. Dewan NA, Rafique S, Kanwar B, Satpathy H, et al. Acute exacerbation of COPD: factorsassociated with poor treatment outcome. Chest March 2000; 117(3): 662-671.

13. Connors AF Jr., Dawson NV, Thomas C, Harrell FE Jr., et al. Outcomes following acuteexacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Studyto Understand Prognoses and Preferences for Outcomes and Risks of Treatments).American Journal of Respiratory and Critical Care Medicine 1996; 154: 959-967.

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18. Anthonisen NR, Manfreda J, Warren CP, Hersfield ES, et al. Antibiotic therapy inexacerbations of chronic obstructive pulmonary disease. Annals of Internal Medicine 1987;106: 196-204.

23

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32. Moayyedi P, Congleton J, Page RL, Pearson SB, et al. Comparison of nebulised salbutamoland ipratropium bromide with salbutamol alone in the treatment of chronic obstructivepulmonary disease. Thorax 1995; 50: 834-837.

33. Fernandez A, Munoz J, de la Calle B, Alia I, et al. Comparison of one versus twobronchodilators in ventilated COPD patients. Intensive Care Medicine 1994; 20: 199-202.

34. Barbera JA, Reyes A, Roco J, Montserrat JM, et al. Effect of intravenously administeredaminophylline on ventiation/perfusion inequaity during recovery from exacerbations ofchronic obstructive pulmonary disease. American Review of Respiratory Disease 1992; 145:1328-1333.

35. Mahon JL, aupacis A, Hodder RV, McKim DA. Theophyline for irreversible chronic airflowlimitation: a randomized study comparing n of 1 trias to standard practice. Chest 1999;115: 38-48.

36. Meyer TJ, Hill NS. Noninvasive positive pressure ventilation to treat respiratory faiure. Annalsof Internal Medicine 1994; 120: 760-770.

37. Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failuredue to restrictive lung disease, COPD, and nocturnal hypoventilation- a consensusconference report. Chest 1999; 116: 521-534.

38. Bott J, Carroll MP, Conway JH, Keilty SE, et al. Randomised controlled trial of nasalventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet1993; 341: 1555-1557.

24

39. Plant PK, Owen JL, Eliott MW. Early use of non-invasive ventilation for acute exacerbationsof chronic obstructive pulmonary disease on general respiratory wards: a multi-centrerandomised controlled trial. Lancet 2000; 355: 1931-1935.

40. Dikensoy O, Ikidag B, Filiz A, Bayram N. Comparison of non-invasive ventilation andstandard medical therapy in acute hypercapnic respiratory failure: a randomisedcontrolled study at a tertiary health center in SE Turkey. International Journal of ClinicalPractice March 2002; 56(2): 85-88.

41. Rizvi N, Mehmood N, Hussain N. Role of Bi-pap in acute respiratory failure due toexacerbation of COPD. Journal of Pakistan Medical Association December 2001; 51(12):414-417.

42. Conti G, Costa R, Maviglia R, Conti M, et al. NIV in the treatment of acute exacerbation ofCOPD and status asthmaticus. Minerva Anestesiologica April 2001; 67(4): 223-227.

43. Vanpee D, Dalaunois L, Gilet JB. Non-invasive positive pressure ventilation for exacerbationof chronic obstructive pulmonary patients in the emergency department. EuropeanJournal of Emergency Medicine March 2001; 8(1): 21-25.

44. Keenan SP, Gregor J, Sibbald WJ, Cook D, et al. Noninvasive positive pressure ventilation inthe setting of severe, acute exacerbations of chronic obstructive pulmonary disease: moreeffective and less expensive. Critical Care Medicine June 2000; 28(6): 2094-2102.

45. Vermeeren MA, Schols AM, Wouter EF. Effects of an acute exacerbation on nutritional andmetabolic profile of patients with COPD. European Respiratory Journal October 1997;10(10): 2264-2269.

46. Saudny-Unterberger H, Martin JG, Gray-Donald K. Impact of nutritional support onfunctional status during an acute exacerbation of chronic obstructive pulmonary disease.American Journal of Respiratory and Critical Care Medicine September 1997; 156(3 Pt 1):794-799.

47. Nevins ML, Epstein SK. Predictors of outcome for patients with COPD requiring invasivemechanical ventilation. Chest June 2001; 119(6): 1840-1849.

48. Vitacca M, Clini E, Porta R, Foglio K, et al. Acute exacerbations in patients with COPD:predictors of need for mechanical ventilation. European Respiratory Journal July 1996; 9(7):1487-1493.

49. Reguero CR, Hamel MB, Davis RB, Desbiens N, et al. A comparison of generalist andpulmonologist care for patients hospitalized with severe chronic obstructive pulmonarydisease: resource intensity, hospital costs, and survival. SUPPORT investigators. Study toUnderstand Prognoses and Preferences for Outcomes and Risks of Treatment. AmericanJournal of Medicine 1998; 105: 366-372.

50. Mushlin AI, Black ER, Connolly CA, Buonaccorso KM, et al. The necessary length of hospitalstay for chronic pulmonary disease. Journal of the American Medical Association 1991;266: 80-83.

51. Sala E, Alegre L, Carrrera M, Ibars M, et al. Supported discharge shortens hospital stay inpatients hospitalized because of an exacerbation of COPD. European Respiratory JournalJune 2001; 17(6): 1138-1142.

52. Skwarska E, Cohen G, Skwarski KM, Lamb C, et al. Randomized controlled trial ofsupported discharge in patients with exacerbations of chronic obstructive pulmonarydisease. Thorax November 2000; 55(11): 907-912.

53. Cotton MM, Bucknall CE, Dagg KD, Johnson MK, et al. Early discharge for patients withexacerbations of chronic obstructive pulmonary disease: a randomized controlled trial.Thorax November 2000; 902-906.

54. The COPD Guidelines Group of the Standards of Care Committee of the BTS. BTS guidelinesfor the management of chronic obstructive pulmonary disease. Thorax 1997; 52 Suppl 5:S1-S28.

55. Lynn J, Ely EW, Zhong Z, McNiff KL, et al. Living and dying with chronic obstructivepulmonary disease. Journal of the American Geriatrics Society May 2000: 48( 5 Suppl): S91-S100.

56. Claessens MT, Lynn J, Zhong Z, Desbiens NA, et al. Dying with lung cancer or chronicobstructive pulmonary disease: insights from SUPPORT. Journal of the American GeriatricsSociety May 2000; 48(5 Suppl): S146-S153.

25

57. McNeely PD, Hebert PC, Dales RE, O’Connor AM, et al. Deciding about mechanicalventilation in end-stage chronic obstructive pulmonary disease: how respirologist perceivetheir role. Canadian Medical Association Journal January 15, 1997; 156(2): 177-183.

58. Siasfakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, et al. Optimalassessment and management of chronic obstructive pulmonary disease (COPD). TheEuropean Respiratory Society Task Force. Eur Respir J 1995; 8:1398-420.

59. American Thoracic Society. Standards for the diagnosis and care of patients with chronicobstructive pulmonary disease. Am J Respir Crit Care Med 1995; 152:S77-121.

60. McCrory DC, Brown C, Selfand SE, Bach PB. Management of exacerbations of COPD: asummary and appraisal of the published evidence. Chest 2001;119:1190-1209.

61. Snow V, Lascher S, Mottur-Pilson C. Evidence base for management of acuteexacerbations of chronic obstructive pulmonary disease. Ann Intern Med 2001;134:595-599.

62. Ferguson GT. Recommendations for the management of COPD. Chest 2000;117:Suppl:23S-28S.

63. Sherk PA, Grossman RF. The chronic obstructive pulmonary disease exacerbation.. ClinChest Med 2000;21:705-721.

64. Wrenn K, Slovis CM, Murphy F, Greenberg RS. Aminophylline therapy for acutebronchospastic disease in the emergency rrom. Ann Intern Med 1991;115:241-247.

65. Rice KL, Leatherman JW, Duane PG, et al. Aminophylline for acute exacerbations ofchronic obstructive pulmonary disease: a controlled trial. Ann Intern Med 1987;107:305-309.

66. Siedenfeld JJ, Jones WN, Moss RE, Trem,per J. Intravenous aminophylline in the treatmentof acute bronchospastic exacerbations of chronic obstructive pulmonary disease. AnnEmerg Med 1984; 13:248-252.

67. Sayiner A, Aytemur ZA, Cirit M, Unsal I. Systemic glucocorticosteroids in severeexacerbations of COPD. Chest 2001;119:726-730.

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APPENDIX SECTION.

APPENDIX 1. SUGGESTED QUESTIONS FOR FOLLOW-UP VISITS OF COPDPATIENTS.

assessment instrument. The validity and reliability of these questionsSuggested Questions for Follow-Up Visits**These questions are examples and do not represent a standardizedassessment instrument. The validity and reliability of these questionshave not been assessed.

Monitor exposure to risk factors: Have you continued to stay off cigarettes? If not, how many cigarettes per day are you smoking? Would you like to quit smoking? Has there been any change in your working

environment?

Monitor disease progression and developmentof complications:

How much can you do before you get short of breath?(Use an everyday example, such as walking up flightsof stairs, up a hill, or on flat ground.)

Has your dyspnea worsened, improved, or stayed thesame since your last visit?

Have you had to reduce your activities because ofdyspnea or other symptoms?

Have any of your symptoms worsened since yourlast visit?

Have you experienced any new symptoms since yourlast visit?

Has your sleep been disrupted due to dyspnea or othersymptoms?

Since your last visit, have you missed any workbecause of your symptoms?

Monitor pharmacotherapy and other medicaltreatment:

What medications are you taking? How often do you take each medication? How much do you take each time? Have you missed or stopped taking any regular doses

of your medications for any reason? Have you had trouble filling your prescriptions

(e.g., for financial reasons, not on formulary)? Please show me how you use your inhaler. Have you tried any other medicines or remedies? Has your medication been effective in controlling

your symptoms? Has your medication caused you any problems?

Monitor exacerbation history: Since your last visit, have you had any episodes/times

when your symptoms were a lot worse than usual? If so, how long did the episode(s) last? What do you

think caused the symptoms to get worse? What didyou do to control the symptoms?

27

REFERENCE:Global Initiative for Chronic Obstructive Lung Disease. Global Strategyfor the Diagnosis, Management, and Prevention of Chronic ObstructivePulmonary Disease. NHLBI/WHO Workshop Report. National Institutes ofHealth. National Heart, Lung, and Blood Institute. Publication Number2701. March 2001.

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APPENDIX 2. BRIEF SMOKING CESSATION INTERVENTION FOR PHYSICIANS

THE THREE MINUTE STRATEGY FOR SMOKING CESSATION INTERVENTION

Tobacco smoking and nicotine addiction is a chronic disease andwithout appropriate interventions, only 2-3% of smokers become non-smokers each year. The primary care physician plays an important andunique role in promoting smoking cessation due to the fact that at least70% of smokers see a physician at least once a year. Moreover, 70% ofsmokers report that they want to quit and have made at least 1 self-described serious quit attempt and cite a physician’s advice as asignificant motivator. Finally, 90% of smokers admit that they would “verylikely” or “somewhat likely” follow their physician’s advice.

With this background, it is important that clinicians are prepared tointervene with tobacco users who are wiling to quit. The five major steps,or the Five A’s are tabulated below. It is important for the clinician to Askeach patient if he or she uses tobacco (Strategy A1), Advise him or her toquit (Strategy A2), Assess willingness to make a quit attempt (Strategy A3),Assist him or her in his quit attempt (Strategy A4) and Arrange for follow upto prevent relapse (Strategy A5).

Patients unwilling to make a quit attempt may lack informationabout the harmful effects of tobacco or may have fears or concernsabout quitting or may be demoralized because of previous relapse. Suchpatients may respond to motivational intervention that provides theclinician an opportunity to educate, reassure and motivate (the Five R’s).Motivational interventions are most likely to be successful when theclinician is empathic, promotes patient autonomy, avoids arguments andsupports the patient’s self-efficacy.

Relapses should not be a source of discouragement as they are therule rather than the exception in smoking cessation. In the TranstheoreticalModel of Change, patients go through the stages of Precontemplation,Contempation, Action and Maintenance in a cyclical manner. Only 5%will go through without ever relapsing. Eighty five percent of patients willcycle back with most of them competing 3 to 4 cycles before they areable to maintain a totally smoke free state. An algorithm is presented tosimplify the suggested steps in smoking cessation intervention.

29

THE “5 A’S” FOR BRIEF INTERVENTION

Strategy A1: ASK

ASK abouttobacco

use

Identify anddocumenttobacco usestatus forevery patientat every visit.

Action Strategies for implementation

Implement anoffice wide systemthat ensures that,for EVERY patient atEVERY clinic visit,tobacco use statusis queried anddocumented.

Expand the vital signs to include tobacco use or use analternative universal identification system.

Alternatives to expanding the vital signs are to placetobacco- use status stickers on all patient charts or toindicate tobacco use status using electronic medicalrecords or computer reminder systems.

VITAL SIGNS

Blood Pressures: _________Pulse: ______ Weight: _________Temperature: _________ RR: _____Tobacco use: Current

FormerNever(circle one)

30

Strategy A2: ADVISE

Advise toquit

In a clear,strong andpersonalizedmanner urgeeverytobacco userto quit.

Action Strategies for implementation

In a clear, strong,and personalizedmanner, urge everytobacco user toquit

Advice should be:

Clear – “ I think it is important for you to quit smokingnow and I can help you”. “ Cutting down while you areill is not enough”.

Strong – “ As your clinician, I need you to know thatquitting smoking is the most important thing you cando to protect your health now and in the future. Theclinic staff and I will help you.

Personalized – Tie the tobacco use to currenthealth/illness, and or its social and economic costs,motivation level / readiness to quit, and /or the impactof tobacco use on children and others in thehousehold.

31

Strategy A3: ASSESS

Assesswillingnessto make aquitattempt.

Is thetobacco userwilling tomake quitattempt atthis time?

Action Strategies for implementation

Ask every tobaccouser if he or she iswilling to make aquit attempt at thistime (e.g., withinthe next 30 days)

Assess patient’s willingness to quit:

If the patient is wiling to make a quit attempt at thistime, provide assistance

If the patient will participate in an intensive treatment,deliver such a treatment or refer to an intensiveintervention

If the patients clearly states he or she is unwilling tomake a quit attempt at this time, provide amotivational intervention

If the patient is member of special population (e.g.,adolescent, pregnant smoker, racial / ethnic minority),consider providing additional information

32

Strategy A4: ASSIST

Assist inquitattempt.

For the patientwiling to make aquit attempt,use counselingandpharmacotherapy to help himor her quit

Action Strategies for implementation

Help the patientwith a quit plan

A patient’s preparation for quitting:

Set a quit date – ideally, the quit date should be within2 weeks

Tell family, friends, and co workers about quitting andrequest understanding and support

Anticipate challenges to planned quit attempt,particularly during the critical first few weeks. Theseinclude nicotine withdrawal symptoms.

Remove tobacco products from your environment.Prior to quitting, avoid smoking in places where youspend a lot of time (e.g., work, home, car)

Providepractical

ABSTINENCE – Total abstinence is essential. “Not even a singlepuff after the quit date”.

33

counseling(problemsolving/skillstraining)

PAST QUIT EXPERIENCE – Identify what helped and what hurtin previous quit attempts.

ANTICIPATE TRIGGERS OR CHALLENGES IN UPCOMINGATTEMPT – Discuss challenges/triggers and how patient willsuccessfully overcome them.

ALCOHOL – Since alcohol can cause relapse, the patientshould consider limiting/abstaining from alcohol whilequitting.

OTHER SMOKERS IN THE HOUSEHOLD – Quitting is more difficultwhen there is another smoker in the household. Patientsshould encourage housemates to quit with them or notsmoke in their presence.

Provide intra-treatment socialsupport

Provide supportive clinical environment while encouragingthe patient in his or her quit attempt. “My office staff and Iare available to assist you.”

Help patientobtain extra-treatment socialsupport

Help patient develop social support for his or her quit attemptin his or her environments outside of treatment. “Ask yourspouse/partner, friends and co-workers to support you in yourquit attempt.”

Recommendthe use ofapproved

Recommend the use of pharmacotherapy found to beeffective. Explain how these medications increase smokingcessation success and reduce withdrawal symptoms. The first-

34

pharmacotherapy

line pharmacotherapy medications include: Bupriopion SR,Nicotine gum, nicotine inhaler, nicotine nasal spray andnicotine patch.

Providesupplementarymaterials

SOURCES – Non-government organizations, local heath units

TYPE – Culturally/racially/educationally/age appropriate forpatient

LOCATION – Readily available at every clinician’s workstation.

Strategy A5: ARRANGE

Arrangefollow up

Schedule followup contactpreferably withinthe first weekafter the quitdate.

Action Strategies for implementation

Schedule follow-up contact,either in personor via telephone

Timing – Follow up contact should occur soon after the quitdate, preferably, during the first week. A second follow upcontact is recommended within the first month. Schedulefurther contacts as indicated.

Actions during follow up contact – Congratulate success. Iftobacco use has occurred, review circumstances and elicitrecommitment to total abstinence. Remind patient that arelapse can be used as a learning experience. Identify

35

problems already encountered and anticipate challenges inthe immediate future. Assess pharmacotherapy use andproblems. Consider use or referral to more intensivetreatment

36

The 5 R’s of MOTIVATIONAL INTERVENTION

Action Strategies for implementation

Relevance

Encourage the patient to indicate why quitting is personallyrelevant, being as specific as possible. Motivational information hasthe greatest impact if it is relevant to patient’s disease status or risk,family or social situation (e.g., having children in the home), healthconcerns, age, gender, and other important patient characteristics(e.g., prior quitting experience, personal barriers to cessation).

Risks

The clinician should ask the patient to identify potential negativeconsequences of tobacco use. The clinician may suggest andhighlight those that seem most relevant to the patient. The clinicianshould emphasize that smoking low – tar / low – nicotine cigarettesor use of other forms of tobacco (e.g., smokeless tobacco, cigars,and pipes) will not eliminate these risks. Examples risks are:

Acute risks: Shortness of breath, exacerbation of asthma,harm to pregnancy, impotence, infertility, increase serumcarbon monoxide.

Long-term risks: Heart attacks and strokes, lung and othercancers (larynx, oral cavity, pharynx, esophagus, pancreas,bladder, cervix), chronic obstructive pulmonary diseases(chronic bronchitis and emphysema), long – term disabilityand need for extended care.

Environmental Risks: Increased risk of lung cancer and heart

37

disease in spouses: higher rate of smoking by children oftobacco users; increased risk for low birth weight, SIDS,asthma, middle ear disease, and respiratory infections inchildren of smokers

Rewards

The clinician should ask the patient to identify potential benefits ofstopping tobacco use. The clinician may suggest and highlight thosethat seem most relevant to the patient. Examples of rewards follow:

Improved health Food will taste better Improved sense of smell Save money Feel better about yourself. Home, car, clothing, breath will smell better Can stop worrying about quitting Set a good example for children Have healthier babies and children Not worry about exposing others to smoke Feel better physically Perform better in physical activities Reduced wrinkling / aging of skin

RoadblocksThe clinician should ask the patient to identify barriers orimpediments to quitting and note elements of treatment ( problemsolving, pharmacotherapy ) that could address barriers.Typical barriers might include:

Withdrawal symptoms Fear of failure Weight gain

38

Lack of support Depression Enjoyment of tobacco

Repetition The motivational intervention should be repeated every time anunmotivated patient visits the clinic setting. Tobacco users who havefailed in previous quit attempts should be told that most peoplemake repeated quit attempts before they are successful.

1

ALGORITHM ON THE SUGGESTED STEPS IN SMOKING CESSATIONINTERVENTION

General Population

Contact With physician

Ask About Smoking

Current Smoker Former SmokerNever Smoker

Precontemplation

Assess stage of Change

Advise to stop smoking

Contemplation

Congratulate andreinforce abstinence

Preparation / Wiling to Quit Now

Motivate: Discuss Concernsand Benefits of Quitting

No Psychiatric orAlcohol Problem

Psychiatric orAlcohol Problem

Arrange Follow-up

Arrange Follow-up Refer

Congratulate andreinforce non-smoking

status

Assist: Set Quit Date, DiscussTreatment Options, Consider

Pharmacotherapy

Succeed Fail (recycle)

Set Quit Date, usecombination therapy with

other agents

FailSucceed

Arrange Follow-upwhen willing to

discuss concerns& benefits of

quitting

2

Reference:Treating Tobacco Use and Dependence. Clinical Practice Guideline. U.S.Department of Health and Human Services. June 2000.

3

APPENDIX 3. COMMONLY ENCOUNTERED DRUGS FOR COPD IN THEPHILIPPINES BY GENERIC NAMES, FORMULATION ANDDOSAGE.

GENERICNAME

FORMULATION QUANTITYPER DOSE

PRESCRIBED DOSAGE ANDFREQUENCY

A. Bronchodilators1. Anti-cholinergic agents

IpratropiumBr

UDV 0.5mg/2mL 1 vial 3 - 4 times a dayPMDI 0.02mg/puff 2 puffs 4 times a day up to 12

puffs/dayInhaled solution 0.025% 2 mL 3-4 times a day

Tiotropium Inhaled caps 18μg/cap 1 cap daily2. Beta-2 agonists

Salbutamolsulfate

syrup 2mg/5mL 2mg to 4 mg every 6 to 8 hourstablet 2mg 1-2 tablets 3-4 times a dayControlled Releasetablet

4mg, 8 mg 1 tab 2 times a day

Pressurized metereddose inhaler (pMDI)

100μg/dose 1-2 puffs every 4 hours, may use2 puffs prn for acute symptoms

nebule 2.5 mg/2.5mL 2.5 mg-5 mg 3-4 times a dayTerbutalinesulfate

syrup 1.5mg/5mL 2 tsp- 1 tbsp every 6 to 8 hourstablet 2.5mg 1 tablet 3-4 times a dayExtended Releasetablet

5mg/ 1 tablet 2 times a day

Inhaled solution 5mg/2mL 2.5 –5 mg every 6 housInhaler 0.25mg/dose 1 –2 puffs every 6 hrsTurbuhaler 500μg/dose 1 – 4 puffs per day up to 4 mg

per dayFenoterol HBr Metered aerosol 0.1mg/dose 1-2 puffs per day up to 8 puffs

per dayProcaterol HClhemihydrate

Tablet 25μg 1-2 tabs 2 times a daySyrup 5μg/mL 10 mL 2 times a daypMDI 10μg/puff 2 puffs every 4 hours and prn

Formoterolfumarate

tablet 40μg 2 tabs 2 times a dayInhaled caps 12μg/cap 1-2 caps per dayTurbuhaler 4.5μg/dose,

9μg/dose1-2 puffs per day max of 4-6 perday

Salmeterol pMDI 25μg/puff 2 - 4 puffs 2 times a dayRotadisk 50μg/blister 1-2 blister 2 times a day

Bambuterol Tablet 10mg/tab 1 tab 1-2 times a dayClenbuterol Tablet 10 ug/tab 1 tab 1-2 times a day

Syrup 5 ug/5ml 10 ml 1-2 times a dayTolubuterol Tablet 1 mg, 2 mg 1-2 tabs 2 times a day

4

3. Methylxanthine derivativesDoxofylline tablet 400mg 1 tab 2 – 3 times a dayTheophylline tablet 130mg 1 tab 3 - 4 times a day

125 mg 1 tab every 6 hours150mg 1 tab 3 - 4 times a day

SR tab 175 mg, 250mg

1 tab every 12 hrs

90, 180 1-2 tabs 2 times aday400 1 tab daily200, 300 1 tab every 12 hrs

Aminophylline ampule 25mg/mL 5mg – 6mg/kg in 20-30 min slowIV infusion

4. Combination anticholinergic with beta-2 agonist agentFenoterolHBr/IpratropiumBr

PMDI 50μg/20μg 1-2 puffs per day max 8 puffsInhaled solution 0.5mg/0.25mg 1 –2 mL 3 –4 times a dayUDV 1.25mg/0.5mg 1 vial up to 4 times a day

IpratropiumBr/Salbutamol

PMDI 21μg/120μg 2 puffs 4 times a day up to 12puffs/day

UDV 500μg/2.5mg 1 vial 3 – 4 times a dayB. Corticosteroids

Beclo-methasone

Inhaler 250μg/dose 200μg to 2000μg day in divideddoses50μg/dose

Rotacap 100μg/capRotadisk 200μg/blistercyclocaps 100μg/cap 100μg – 400μg 2 times a day

Fluticasonepropionate

Inhaler 50μg/dose,12μg/dose125μg/dose

100μg – 1000μg 2 times a day

Rotadisk 50μg/doseNebule 500μg/2mL 500μg – 2000μg 2 times a day

Budesonide inhaler 100μg/dose200μg/dose

400μg - 2400μg per day dividedin 2 to 4 doses

Turbuhaler 100μg/dose200μg/dose

Respules 250μg/mL500μg/mL

Prednisone tablet 2.5 mg, 5 mg,7.5 mg, 10 mg30 mg

20mg – 60 mg daily

Prednisolone Syrup 15 mg/5ml 30-60 mg/dayBetamethasone Tablet 500 ug 2-3 mg dailyDexamethasone Tablet 500 ug,750 ug,

3 mg, 4 mg0.5-10 mg daily

Vial 4mg, 5 mg/ml 0.05-0.2 mg/kg body weight

5

Methyl-prednisolone

Tablet 4 mg, 16 mg 4-48 mg/dayVial 125 mg/2ml

500 mg/7.7 ml1 gm/ 16 ml

10-40 mg every 4-6 hours IV orIM for 48-72 hours

Hydrocortisone vial 100mg, 250mg/2 mL

150 mg to 300 mg daily individed doses

C. ExpectorantsAmbroxol HCl Tablet 30 mg 1 tab 3 times a day

ER tablet 75 mg 1 tab dailySyrup 15 mg/5ml 1 tsp 3 times a dayInhalation solution 15 mg/2ml 1-2 inhalations of 2-3 ml solution

dailyVial 15 mg/2ml 1-2 amps 2-3times a day IV or

IMAcetylcysteine Effervescent tab 600 mg 600 mg daily or 200 mg 3 times

a daysachet 100 mg200 mg

granules 100 mg/5mlInhalation solution 100 mg/mL 1 amp 1 – 2 times daily

Bromhexine Tablet 8 mg, 16 mg 1 tab 3 times a daySyrup 4 mg/5ml 2 tsp 3 times a dayInhalation solution 2 mg/ml 4 ml of solution diluted 1:1 with

normal saline inhale every 12hours

Vial 4mg 1 ampule SC, IM, IV every 8-12hours

Carbocisteine capsule 250 mg 500 mg 3 times a day500 mg

Syrup 250 mg/5ml 10 ml 3 times a dayErdosteine Capsule 300mg 1 cap 2 times a dayGuiafenesin Syrup 100 mg/5 ml 5-10 ml 3-4 times a dayLagundi leaves Tablet 300mg, 600 mg 300-600 mg 3-4 times a dayMesna Inhalation or

Instillation solution200 mg/ml 1-2 amps inhalation 1-4 x a day

1-2 ml diluted with equal volumeof distilled water or saline hourlyinto the endotracheal tube ortracheotomy cannula untilfluiditication and evacuation ofsecretions

D. Other medicationsLyophilizedbacterialextract

capsule 7 mg 1 cap daily for at least ten days

Influenzavaccine

Pre-filled syringe 0.5 mL Administer IM once a year

6

Pneumococcalvaccine

vial 0.5 mL Administer SC or IM

7

APPENDIX 4. LIST OF AVAILABLE PULMONARY REHABILITATIONPROGRAM SERVICES IN THE PHILIPPINES:

1. Lung Center of the Philippines2. Perpetual Help Medical Center, Las Pinas3. Philippine General Hospital4. Philippine Heart Center for Asia5. St. Luke’s Medical Center6. The Medical City7. University of Santo Tomas Hospital8. Veteran’s Memorial Medical Center